CNS Drugs

, Volume 2, Issue 1, pp 40–77 | Cite as

New Antiepileptic Drugs

A Review of Their Current Status and Clinical Potential
  • Philip N. Patsalos
  • John S. Duncan
Drug Therapy

Summary

Approximately 20 to 30% of patients with newly diagnosed epilepsy do not have their seizures controlled with currently available antiepileptic drugs. The clinical need for new antiepileptic drugs is therefore clear.

In recent years, as our understanding of the molecular basis of epilepsy has unfolded, several novel candidate antiepileptic drugs have become available for clinical evaluation. The major emphasis has been on the development of more potent and effective antiepileptic drugs, and also drugs with fewer adverse effects than existing therapies. This has resulted in 7 new drugs being licenced around the world in the last 5 years (felbamate, gabapentin, lamotrigine, oxcarbazepine, piracetam, vigabatrin and zonisamide). In addition, 7 other promising drugs are in various stages of development [eterobarb, fosphenytoin, levetiracetam (ubc L059), remacemide, stiripentol, tiagabine and topiramate].

Numerous advantages over existing antiepileptic drugs can be identified for some of these new drugs. A mechanism of action has been determined for lamotrigine, tiagabine and vigabatrin. This may prove particularly useful therapeutically since it allows a more rational treatment strategy. Eterobarb, fosphenytoin, oxcarbazepine and remacemide are prodrugs. This is a particular advantage for fosphenytoin, which is metabolised to phenytoin. Gabapentin, piracetam and topiramate are not metabolised and vigabatrin is minimally metabolised. These drugs do not exhibit significant binding to blood proteins. Therefore, these drugs are not susceptible to significant pharmacokinetic drug interactions. Oxcarbazepine also exhibits minimal drug interactions. This is in contrast to felbamate, lamotrigine and stiripentol, drugs with which pharmacokinetic interactions can be clinically problematic.

All drugs, with the exception of piracetam, are effective treatments for partial or secondarily generalised seizures. Piracetam and zonisamide are effective in myoclonus, and felbamate has been licenced for use in children with Lennox-Gastaut syndrome. All 14 drugs have the potential to induce adverse effects, mostly CNS-related. Whilst treatment recommendations can be made for some of the drugs, these cannot be considered definitive since they are based largely on data from controlled clinical studies in highly selected patients. Further treatment recommendations for different seizure types and epilepsy syndromes will inevitably develop as clinical experience with the drugs increases.

Keywords

Gabapentin Antiepileptic Drug Lamotrigine Vigabatrin Oxcarbazepine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Goodridge DMG, Shorvon SD. Epileptic seizures in a population of 6000: II: treatment and prognosis. BMJ 1983; 187: 645–7Google Scholar
  2. 2.
    Sander JWAS, Shorvon SD. Incidence and prevalence studies in epilepsy and their methodological problems: a review. J Neurol Neurosurg Psychiatry 1987; 50: 829–39PubMedGoogle Scholar
  3. 3.
    O’Leary JL, Goldring S. Science and epilepsy: neuroscience gains in epilepsy research. New York: Raven Press, 1976Google Scholar
  4. 4.
    Temkin O. The falling sickness. A history of epilepsy from the Greeks to the beginning of modern neurology. 2nd ed. Baltimore: Johns Hopkins University Press, 1971Google Scholar
  5. 5.
    Locock C. Discussion of paper by Sieveking EH, Analysis of 52 cases of epilepsy observed by author. Lancet 1857; 1: 527Google Scholar
  6. 6.
    Hauptmann A. Luminal bei epilepsie. Munch Med Wochenschr 1912; 59: 1907–9Google Scholar
  7. 7.
    Merritt HH, Putnam TJ. Sodium diphenylhydantoinate in treatment of convulsive disorders. JAMA 1938; 111: 1068–73Google Scholar
  8. 8.
    Reynolds EH, Chadwick DW, Galbraith AW. One drug (phenytoin) in the treatment of epilepsy. Lancet 1976; 1: 923–6PubMedGoogle Scholar
  9. 9.
    Reynolds EH, Shorvon SD. Monotherapy or poly therapy for epilepsy. Epilepsia 1981; 22: 1–10PubMedGoogle Scholar
  10. 10.
    Shorvon SD, Reynolds EH. Early prognosis of epilepsy. BMJ 1982; 285: 1699–701PubMedGoogle Scholar
  11. 11.
    Patsalos PN, Duncan JS. Antiepileptic drugs: a review of clinically significant drug interactions. Drug Saf 1993; 9: 156–84PubMedGoogle Scholar
  12. 12.
    Brown GR, Miyata M, McCormack JP. Drug concentration monitoring. An approach to rational use. Clin Pharmacokinet 1993; 24: 187–94PubMedGoogle Scholar
  13. 13.
    Choonara IA, Rane A, Therapeutic drug monitoring of anticonvulsants. State of the art. Clin Pharmacokinet 1990; 18: 318–28PubMedGoogle Scholar
  14. 14.
    Patsalos PN. New antiepileptic drug formulations for the management of epilepsy. In: Clifford Rose F, editor. Advances in neuropharmacology. London: Smith-Gordon & Co., 1993: 125–37Google Scholar
  15. 15.
    Fariello RG, Forchetti CM, Fisher RJ. GABAergic function in relation to seizure phenomena. In: Fisher RS, Coyle JT, editors. Neurotransmitters and epilepsy. New York: Wiley-Liss, 1991: 77–94Google Scholar
  16. 16.
    Dingledine R, McBain CJ, McNamara JD. Excitatory amino acid receptor in epilepsy. Trends Neurosci 1990; 11: 334–8Google Scholar
  17. 17.
    During MJ, Spencer DD. Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 1993; 341: 1607–10PubMedGoogle Scholar
  18. 18.
    Marescaux C, Vergnes M, Bernasconi R. GABAB receptor antagonists: potential new anti-absence drugs. J Neural Transm 1992; Suppl 35: 179–88Google Scholar
  19. 19.
    Fisher RS. Glutamate and epilepsy. In: Fisher RS, Coyle JT, editors. Neurotransmitters and epilepsy. New York: Wiley-Liss, 1991: 131–45Google Scholar
  20. 20.
    Baker GA, Smith DF, Dawey M, et al. The initial development of a health-related quality of life model as an outcome measure in epilepsy. Epilepsy Res 1993; 16: 65–81PubMedGoogle Scholar
  21. 21.
    Duncan JS, Sander JWAS. The Chalfont Seizure Severity Scale. J Neurol Neurosurg Psychiatry 1991; 54: 873–6PubMedGoogle Scholar
  22. 22.
    Jacoby A, Baker G, Smith D, et al. Measuring the impact of epilepsy: the development of a novel scale. Epilepsy Res 1993; 16: 83–8PubMedGoogle Scholar
  23. 23.
    Rapaport RL, Kupferberg HJ. Metabolism of dimethoxymethylphenobarbital in mice. Relationship between brain phenobarbital levels and anticonvulsant activity. J Med Chem 1973; 16: 599–602Google Scholar
  24. 24.
    Baumel I, Gallagher B, Di Micco J, et al. Metabolism, distribution and anticonvulsant properties of N, N-dimethoxymethylphenobarbital in the rat. J Pharmacol Exp Ther 1976; 196: 180–7PubMedGoogle Scholar
  25. 25.
    Gallagher BB. Eterobarb. In: Levy R, Mattson R, Meldrum B, et al., editors. Antiepileptic drugs. New York: Raven Press, 1989: 103–15Google Scholar
  26. 26.
    Mutsumoto H, Gallagher B. Metabolism and excretion of C14-eterobarb in epilepsy patients. In; Janz D. editor. Epileptology. Stuttgart: George Thiene, 1976: 122–9Google Scholar
  27. 27.
    Goldberg MA, Gal J, Cho AK, et al. Metabolism of dimethoxymethyl phenobarbital (eterobarb) in patients with epilepsy. Ann Neurol 1979; 5: 121–6PubMedGoogle Scholar
  28. 28.
    Gallagher BB, Baumel I, Woodbury S, et al. Clinical evaluation of eterobarb, a new anticonvulsant. Neurology 1975; 25: 399–404PubMedGoogle Scholar
  29. 29.
    Gallagher BB, Woodbury D. A double-blind comparison of the anticonvulsants eterobarb and phenobarbital. In: Janz D, editor. Epileptology. Stuttgart: George Thieme, 1976: 117–22Google Scholar
  30. 30.
    Mattson R, Williamson P, Hanahan E. Eterobarb (DMMP) therapy in epilepsy. Neurology 1976; 26: 1014–7PubMedGoogle Scholar
  31. 31.
    Smith D. A clinical evaluation of eterobarb in epileptic children. In: Meinardi H, Rowan AJ, editors. Advances in epileptology. Amsterdam: Swetz and Zeitlinger, 1977: 318–21Google Scholar
  32. 32.
    Smith DB, Goldstein SG, Roomet A. A comparison of the toxicity effects of the anticonvulsant eterobarb (Antilon, DMMP) and phenobarbital in normal human volunteers. Epilepsia 1986; 27: 149–55PubMedGoogle Scholar
  33. 33.
    Wolter KD. Eterobarb. In: Pisani F, Perucca E, Avanzini G, editors. New antiepileptic drugs. Epilepsy Research Suppl. 3. Amsterdam: Elsevier Science Publishers, 1991: 99–102Google Scholar
  34. 34.
    Swinyard EA, Sofia RK, Kupferberg HJ. Comparative anticonvulsant activity and neurotoxicity of felbamate and four prototype antiepileptic drugs in mice and rats. Epilepsia 1986; 27: 27–34PubMedGoogle Scholar
  35. 35.
    Swinyard EA, Woodhead JH, Franklin MR, et al. The effect of chronic felbamate administration on anticonvulsant activity and hepatic drug-metabolizing enzymes in mice and rats. Epilepsia 1987; 28: 295–300PubMedGoogle Scholar
  36. 36.
    Sofia RD, Kramer L, Perhach JL, et al. Felbamate. In: Pisani F, Perucca E, Avanzini G, et al., editors. New antiepileptic drugs. Epilepsy Research Suppl. 3. Amsterdam: Elsevier Science Publishers, 1991: 103–8Google Scholar
  37. 37.
    White HS, Wolf HH, Swinyard EA, et al. A neuropharmacological evaluation of felbamate as a novel anticonvulsant. Epilepsia 1992; 33: 564–72PubMedGoogle Scholar
  38. 38.
    Rho JM, Donevan SD, Rogawski MA. Mechanism of action of the anticonvulsant felbamate: opposing effects on N-methyl-D-aspartate and γ-aminobutyric acid A receptors. Ann Neurol 1994; 35: 229–34PubMedGoogle Scholar
  39. 39.
    Gordon R, Gels M, Wichmann J, et al. Interaction of felbamate with several other antiepileptic drugs against seizures induced by maximal electroshock in mice. Epilepsia 1993; 34: 367–71PubMedGoogle Scholar
  40. 40.
    Chronopoulos A, Stafstrom C, Thurber S, et al. Neuroprotective effect of felbamate after kainic acid-induced status epilepticus. Epilepsia 1993; 34: 359–66PubMedGoogle Scholar
  41. 41.
    McCabe RT, Wasterlain CG, Kucharczyk N, et al. Evidence for anticonvulsant and neuroprotective action of felbamate mediated by strychnine-insensitive glycine receptors. J Pharmacol Exp Ther 1993; 264: 1248–52PubMedGoogle Scholar
  42. 42.
    Wallis RA, Panizzon KL. Glycine reversal of felbamate hypoxic protection. Neuroreport 1993; 4: 951–4PubMedGoogle Scholar
  43. 43.
    Wasterlain CG, Adams LM, Schwartz PH, et al. Posthypoxic treatment with felbamate is neuroprotective in a rat model of hypoxic-ischemia. Neurology 1993; 43: 2303–10PubMedGoogle Scholar
  44. 44.
    Wilensky AJ, Friel PN, Ojemann LM, et al. Pharmacokinetics of W-554 (ADD 03055) in epileptic patients. Epilepsia 1985; 26: 602–6PubMedGoogle Scholar
  45. 45.
    Ausumalli VE, Wong KK, Kucharczyk N, et al. Felbamate in vitro metabolism by rat liver microsomes. Drug Metab Dispos 1991; 19: 1135–8Google Scholar
  46. 46.
    Perhatch JL, Weliky I, Newton JJ, et al. Felbamate. In: Meldrum BS, Porter RJ, editors. New anticonvulsant drugs. London: J Libbey & Co., 1986: 117–25Google Scholar
  47. 47.
    Fuerst RH, Graves NM, Leppik IE, et al. Felbamate increases phenytoin but decreases carbamazepine concentrations. Epilepsia 1988; 29: 488–91PubMedGoogle Scholar
  48. 48.
    Graves NM, Holmes GB, Fuerst RH, et al. Effect of felbamate on phenytoin and carbamazepine serum concentrations. Epilepsia 1989; 30: 225–9PubMedGoogle Scholar
  49. 49.
    Sheridan PH, Ashworth M, Milne K, et al. Open pilot study of felbamate in partial seizures [abstract]. Epilepsia 1986; 27: 649Google Scholar
  50. 50.
    Wagner ML, Graves NM, Marienan K, et al. Discontinuation of phenytoin and carbamazepine in patients receiving felbamate. Epilepsia 1991; 32: 398–406PubMedGoogle Scholar
  51. 51.
    Albani F, Theodore WH, Washington P, et al. Effect of felbamate on plasma levels of carbamazepine and its metabolites. Epilepsia 1991; 32: 130–2PubMedGoogle Scholar
  52. 52.
    Wagner ML, Remmel RP, Graves NM, et al. Effect of felbamate on carbamazepine and its major metabolites. Clin Pharmacol Ther 1993; 53: 536–43PubMedGoogle Scholar
  53. 53.
    Wagner ML, Graves NM, Leppik IE, et al. The effect of felbamate on valproate disposition [abstract]. Epilepsia 1991; 32Suppl. 3: 15Google Scholar
  54. 54.
    Leppik IE, Dreifuss FE, Pledge GW, et al. Felbamate for partial seizures: results of a controlled clinical trial. Neurology 1991; 41: 1785–9PubMedGoogle Scholar
  55. 55.
    Theodore WH, Raubertas RF, Porter RJ, et al. Felbamate: a clinical trial for complex partial seizures. Epilepsia 1991; 32: 392–7PubMedGoogle Scholar
  56. 56.
    Bourgeois BFD, Leppik IE, Sackellares JC, et al. Felbamate: a double-blind controlled trial in patients undergoing presurgical evaluation of partial seizures. Neurology 1993; 43: 693–6PubMedGoogle Scholar
  57. 57.
    Faught E, Sachdeo RC, Remler MP, et al. Felbamate monotherapy for partial-onset seizures: an active-control trial. Neurology 1993; 43: 688–92PubMedGoogle Scholar
  58. 58.
    Sachdeo R, Kramer LD, Rosenberg A, et al. Felbamate monotherapy: controlled trial in patients with partial onset seizures. Ann Neurol 1992; 32: 386–92PubMedGoogle Scholar
  59. 59.
    Ritter FJ, Leppik IE, Dreifuss FE, et al. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut Syndrome). N Engl J Med 1993; 328: 29–33Google Scholar
  60. 60.
    Dodson WE. Felbamate in the treatment of Lennox-Gastaut Syndrome: results of a 12 month open-label study following a randomized clinical trial. Epilepsia 1993; 34Suppl. 7: SI8–24Google Scholar
  61. 61.
    MacDonald RL. Antiepileptic drug actions. Epilepsia 1989; 30Suppl. 1: SI9–28Google Scholar
  62. 62.
    Boucher BA, Bombassaro AM, Rasmussen SN, et al. Phenytoin pro-drug 3-phosphoryloxymethyl phenytoin (ACC-9653): pharmacokinetics in patients following intravenous and intramuscular administration. J Pharm Sci 1989; 78: 929–32PubMedGoogle Scholar
  63. 63.
    Gerber N, Mays DC, Donn KH, et al. Safety, tolerance and pharmacokinetics of intravenous doses of phosphate ester of 3-hydroxymethyl-5,5-disphenylhydantoin: a new prodrug of phenytoin. J Clin Pharmacol 1988; 28: 1023–32PubMedGoogle Scholar
  64. 64.
    Jamerson BD, Donn KH, Dukes GE, et al. Absolute bioavailability of phenytoin after 3-phosphoryloxymethyl phenytoin disodium (ACC-9653) administration to humans. Epilepsia 1990; 31: 592–7PubMedGoogle Scholar
  65. 65.
    Leppik IE, Boucher BA, Wilder BJ, et al. Pharmacokinetics and safety of a phenytoin pro-drug given IV and IM in patients. Neurology 1990; 40: 456–60PubMedGoogle Scholar
  66. 66.
    Earnest MP, Marx JA, Drury LR. Complications of intravenous phenytoin for acute treatment of seizures. JAMA 1983; 249: 762–5PubMedGoogle Scholar
  67. 67.
    Louis S, Kutt H, McDowell F. The cardiocirculatory changes caused by intravenous Dilantin and its solvents. Am Heart J 1967; 74: 523–9PubMedGoogle Scholar
  68. 68.
    Zoneraich S, Zoneraich O, Siegal J. Sudden death following intravenous sodium diphenylhydantoin. Am Heart J 1976; 91: 375–7PubMedGoogle Scholar
  69. 69.
    Dean JC, Smith KR, Boucher BA, et al. Safety, tolerance, and pharmacokinetics of intramuscular fosphenytoin, a phenytoin pro-drug, in neurosurgery patients [abstract]. Epilepsia 1993; 34Suppl. 6: 111Google Scholar
  70. 70.
    Legarda S, Maria BL, Mutsuo F, et al. Safety, tolerance, and pharmacokinetics of fosphenytoin, a phenytoin pro-drug, in status epilepticus [abstract]. Epilepsia 1993; 34Suppl. 6: 60Google Scholar
  71. 71.
    Rock DM, Kelly M, McDonald RL. Gabapentin actions on ligand- and voltage-gated responses in cultured rodent neurons. Epilepsy Res 1993; 16: 89–98PubMedGoogle Scholar
  72. 72.
    Gotz E, Feuerstein TJ, Lais A, et al. Effects of gabapentin on release of γ-aminobutyric acid from slices of rat neostriatum. Arzneimittelforschung 1993; 43: 636–7PubMedGoogle Scholar
  73. 73.
    Loscher W, Honack D, Taylor CP. Gabapentin increases aminooxyacetic acid-induced GAB A accumulation in several regions of rat brain. Neurosci Lett 1991; 128: 150–4PubMedGoogle Scholar
  74. 74.
    Wamil AW, McLean MJ. Limitation by gabapentin of high frequency action potential firing by mouse central neurons in cell culture. Epilepsy Res 1994; 17: 1–11PubMedGoogle Scholar
  75. 75.
    Hill DR, Suman-Chauhan N, Woodruff GN. Localization of [3H] gabapentin to a novel site in rat brain: autoradiographic studies. Eur J Pharmacol 1993; 244: 303–9PubMedGoogle Scholar
  76. 76.
    Suman-Chauhan N, Webdale L, Hill DR, et al. Characterisation of [3H]-gabapentin binding site to a novel site in rat brain: homogenate binding studies. Eur J Pharmacol (Mol Pharmacol Sec) 1993; 244: 293–301Google Scholar
  77. 77.
    Taylor CP, Vartanian MG, Yuen PW, et al. Potent and stereospecific anticonvulsant activity of 3-isobutyl GAB A relates to in vitro binding at a novel site labelled by tritiated gabapentin. Epilepsy Res 1993; 14: 11–5PubMedGoogle Scholar
  78. 78.
    Bartoszyk GD, Meyerson N, Reimann W, et al. Gabapentin. In: Meldrum BS, Porter RJ, editors. New anticonvulsant drugs. London: John Libbey, 1986: 147–63Google Scholar
  79. 79.
    Kondo T, Fromm GH, Schmidt B. Comparison of gabapentin with other antiepileptic and GABAergic drugs. Epilepsy Res 1991; 8: 226–31PubMedGoogle Scholar
  80. 80.
    Shotwell MA, Jayne DW, Kilberg MS, et al. Neutral amino acid transport systems in Chinese hamster ovary cells. J Biol Chem 1990; 256: 5422–7Google Scholar
  81. 81.
    Stewart BH, Kugler AR, Thompson PR, et al. A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma. Pharm Res 1993; 10: 276–81PubMedGoogle Scholar
  82. 82.
    Vollmer KO, von Hodenberg A, Kolle EU. Pharmacokinetics and metabolism of gabapentin in rat, dog and man. Arzneimittelforschung 1986; 36: 830–9PubMedGoogle Scholar
  83. 83.
    Ben-Menachem E, Persson LI, Hedner T. Selected CSF biochemistry and gabapentin concentration in the CSF and plasma in patients with partial seizures after a single oral dose of gabapentin. Epilepsy Res 1992; 11: 45–9PubMedGoogle Scholar
  84. 84.
    Pardridge WM, Choi TB, editors. Neutral amino acid transport at the humans blood-brain barrier. Fed Proc 1988; 45: 2073–8Google Scholar
  85. 85.
    Erecinsk M, Silver IA. Metabolism and role of glutamate in mammalian brain. Prog Neurobiol 1990; 35: 245–96Google Scholar
  86. 86.
    Torgner I, Kvamme E. Synthesis of transmitter glutamate and glial-neuron interrelationship. Mol Chem Neuropathol 1989; 12: 11–5Google Scholar
  87. 87.
    Welty DF, Schielke GP, Vartanian MG, et al. Gabapentin anticonvulsant action in rats: disequilibrium with peak drug concentrations in plasma and brain microdialysate. Epilepsy Res 1993; 16: 175–81PubMedGoogle Scholar
  88. 88.
    Ben-Menachem E, Hamberger A, Mumford J. Effect of long-term vigabatrin therapy on GABA and other amino acid concentrations in the central nervous system - a case study. Epilepsy Res 1993; 16: 241–3PubMedGoogle Scholar
  89. 89.
    Schmidt B. Potential antiepileptic drugs. Gabapentin. In: Levy RH, Dreifuss FE, Mattson RH, et al., editors. Antiepileptic drugs, 3rd ed. New York: Raven Press, 1989: 925–35Google Scholar
  90. 90.
    Bockbrader HN, Radulovic LL, Loewen G, et al. Lack of drug interactions between Neurontin (gabapentin) and other antiepileptic drugs [abstract]. Epilepsia 1993; 34 Suppl. 2: 158Google Scholar
  91. 91.
    Busch JA, Bockbrader HN, Randinitis EJ, et al. Lack of clinically significant drug interactions with Neurontin (gabapentin) [abstract]. Epilepsia 1993; 34Suppl. 2: 158Google Scholar
  92. 92.
    Hooper WD, Kavanagh MC, Herkes GK, et al. Lack of a pharmacokinetic interaction between phenobarbitone and gabapentin. Br J Clin Pharmacol 1991; 31: 171–4PubMedGoogle Scholar
  93. 93.
    Radulovic LL, Wilder BJ, Leppik IE, et al. Lack of interaction of gabapentin with carbamazepine or valproate. Epilepsia 1994; 35: 155–61PubMedGoogle Scholar
  94. 94.
    Richens A. Clinical pharmacokinetics of gabapentin. In: Chadwick D, editor. New trends in epilepsy management epilepsy. London: Royal Society of Medicine Services, 1993: 41–6Google Scholar
  95. 95.
    Crawford P, Ghadiali E, Lane R, et al. Gabapentin as an antiepileptic drug in man. J Neurol Neurosurg Psychiatry 1987; 50: 682–6PubMedGoogle Scholar
  96. 96.
    Andrews J, Chadwick D, Bates D, et al. Gabapentin in partial seizures. Lancet 1990; 335: 1114–7Google Scholar
  97. 97.
    Sivenius J, Kalviainen R, Ylinen A, et al. Double-blind study of gabapentin in the treatment of partial seizures. Epilepsia 1991; 32: 539–42PubMedGoogle Scholar
  98. 98.
    Ojemann LM, Wilenski AJ, Temkin NR, et al. Long-term treatment with gabapentin for partial seizures. Epilepsy Res 1992; 13: 159–65PubMedGoogle Scholar
  99. 99.
    Oommen K, Penry JK, Riela A, et al. Gabapentin as add-on therapy in refractory partial epilepsy: a double-blind, placebo-controlled, parallel-group study. Neurology 1993; 43: 2292–8Google Scholar
  100. 100.
    Saletu B, Grunberger J, Linzmayer L. Evaluation of encephalotropic and psychotropic properties of gabapentin in man by pharmaco-EEG and psychometry. Int J Clin Pharmacol Ther Toxicol 1986; 24: 362–73PubMedGoogle Scholar
  101. 101.
    Leach M, Marden C, Miller AA. Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action. Epilepsia 1988; 27: 490–7Google Scholar
  102. 102.
    Leach MJ, Baxter MG, Crichley MA. Neurochemical and behavioural aspects of lamotrigine. Epilepsia 1991; 32Suppl. 2: S4–9PubMedGoogle Scholar
  103. 103.
    Lees G, Leach MJ. Studies on the mechanism of action of the novel anticonvulsant lamotrigine (Lamictal) using primary neuroglial cultures from rat cortex. Brain Res 1993; 612: 190–9PubMedGoogle Scholar
  104. 104.
    Smith SE, Al-Zubaidy ZA, Chapman AG, et al. Excitatory amino acid antagonists, lamotrigine and BW 1003C87 as anticonvulsants in the genetically epilepsy-prone rat. Epilepsy Res 1993; 15: 101–11PubMedGoogle Scholar
  105. 105.
    Cohen AF, Land GS, Breimer DD, et al. Lamotrigine, a new anticonvulsant: pharmacokinetics in normal humans. Clin Pharmacol Ther 1987; 42: 535–41PubMedGoogle Scholar
  106. 106.
    Posner J, Holdich T, Crome P. Comparison of lamotrigine pharmacokinetics in young and elderly healthy volunteers. J PharmMed 1991; 1: 121–8Google Scholar
  107. 107.
    Yuen A. Lamotrigine. In: Pisani F, Perucca E, Aranzini G, et al. editors. New antiepileptic drugs. Amsterdam: Elsevier Science Publishers, 1991: 115–23Google Scholar
  108. 108.
    Ramsay RE, Pellock JM, Garnett WR, et al. Pharmacokinetics and safety of lamotrigine (Lamictal) in patients with epilepsy. Epilepsy Res 1991; 10: 191–200PubMedGoogle Scholar
  109. 109.
    Messenheimer J, Ramsay RE, Willmore LJ, et al. Lamotrigine therapy for partial seizures: a multicenter, placebo-controlled, double-blind, cross-over trial. Epilepsia 1994; 35: 113–21PubMedGoogle Scholar
  110. 110.
    Buckley NA, Whyte IM, Dawson AH. Self-poisoning with lamotrigine. Lancet 1993; 342: 1552–3PubMedGoogle Scholar
  111. 111.
    Yau MK, Adams MA, Wargin WA, et al. A single dose and steady-state pharmacokinetic study of lamotrigine in healthy volunteers [abstract]. Third International Cleveland Clinic Bethal Symposium; 1992 June 16-20: ClevelandGoogle Scholar
  112. 112.
    Binnie CD, Van Emde Boas W, Kasteleijn-Nols-Trenite DGA, et al. Acute effects of lamotrigine (BW430C) in persons with epilepsy. Epilepsia 1986; 27: 248–54PubMedGoogle Scholar
  113. 113.
    Jawad S, Yuen W, Peck A, et al. Lamotrigine: single-dose pharmacokinetics and initial 1 week experience in refractory epilepsy. Epilepsy Res 1987; 1: 194–201PubMedGoogle Scholar
  114. 114.
    Warner T, Patsalos PN, Prevett M, et al. Lamotrigine induced carbamazepine toxicity: an interaction with carbamazepine-10,11-epoxide. Epilepsy Res 1992; 11: 147–50PubMedGoogle Scholar
  115. 115.
    Wolf P. Lamotrigine: preliminary clinical observations on pharmacokinetics and interactions with traditional antiepileptic drugs. J Epilepsy 1992; 5: 73–9Google Scholar
  116. 116.
    Jawad S, Oxley J, Yuen W, et al. The effect of lamotrigine, a novel anticonvulsant on interictal spikes in patients with epilepsy. Br J Clin Pharmacol 1986; 22: 191–3PubMedGoogle Scholar
  117. 117.
    Jawad S, Richens A, Yuen W. Controlled trial of lamotrigine for refractory partial epilepsy. Epilepsia 1989; 30: 356–63PubMedGoogle Scholar
  118. 118.
    Binnie CD, Debets RMC, Engelman M, et al. Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy. Epilepsy Res 1989; 4: 222–9PubMedGoogle Scholar
  119. 119.
    Sander JWAS, Patsalos PN, Oxley JR, et al. A randomised double-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy. Epilepsy Res 1989; 4: 222–9Google Scholar
  120. 120.
    Loiseau P, Yuen W, Duche B, et al. A randomised, double-blind, placebo-controlled, crossover, add-on trial of lamotrigine in patients with treatment-resistant partial seizures. Epilepsy Res 1990; 7: 136–45PubMedGoogle Scholar
  121. 121.
    Matsuo F, Bergen D, Faught E, et al. Placebo-controlled study of the efficacy and safety of lamotrigine in patients with partial seizures. Neurology 1993; 43: 2284–91PubMedGoogle Scholar
  122. 122.
    Sander JWAS, Trevisol-Bittencourt PC, Hart YM, et al. The efficacy and long-term tolerability of lamotrigine in the treatment of severe epilepsy. Epilepsy Res 1990; 7: 226–9PubMedGoogle Scholar
  123. 123.
    Schapel GJ, Beran RG, Vajdor FJE, et al. Double-blind, placebo controlled, crossover study of lamotrigine in treatment resistant partial seizures. J Neurol Neurosurg Psychiatry 1993; 56: 448–53PubMedGoogle Scholar
  124. 124.
    Smith D, Baker G, Davies G, et al. Randomised, placebo-controlled, double-blind, crossover trial of lamotrigine as add-on therapy in patients with refractory epilepsy [abstract]. Epilepsia 1991; 32Suppl. 1: 59Google Scholar
  125. 125.
    Smith D, Baker G, Davies G, et al. Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsia 1993; 34: 312–22PubMedGoogle Scholar
  126. 126.
    Binnie CD. An overview: efficacy of lamotrigine. In: Richens A, editor. Clinical update on lamotrigine: a novel antiepileptic agent. Royal Tunbridge Wells: Wells Medical Ltd., 1992: 31–7Google Scholar
  127. 127.
    Pisani F, Gallitto G, Di Perri R. Could lamotrigine be useful in status epilepticus? A case report. J Neurol Neurosurg Psychiatry 1991; 54: 845–6PubMedGoogle Scholar
  128. 128.
    Sander JWAS, Hart YM, Patsalos PN, et al. Lamotrigine and generalised seizures [abstract]. Epilepsia 1991; 32 Suppl. 1: 59Google Scholar
  129. 129.
    Stewart J, Hughes E, Reynolds EH. Lamotrigine for generalized epilepsies [abstract]. Lancet 1992; 340: 1223PubMedGoogle Scholar
  130. 130.
    Timmings PL, Richens A. Lamotrigine in primary generalized epilepsy. Lancet 1992; 339: 1300–1PubMedGoogle Scholar
  131. 131.
    Hosking G, Spencer S, Yuen AWC. Lamotrigine in children with severe developmental abnormalities in a paediatric population with refractory seizures [abstract]. Epilepsia 1993; 34Suppl. 6: 42Google Scholar
  132. 132.
    Schlumberger E, Chavez F, Palacios L, et al. Lamotrigine in treatment of 120 children with epilepsy. Epilepsia 1994; 35: 359–67PubMedGoogle Scholar
  133. 133.
    Betts T, Goodwin G, Withers RM, et al. Human safety of lamotrigine. Epilepsia 1991; 32Suppl. 2: S17–21PubMedGoogle Scholar
  134. 134.
    Yuen A. Safety issues. In: Richens A, editor. Clinical update on lamotrigine: a novel antiepileptic agent. Tunbridge Wells: Wells Medical Ltd., 1992: 69–75Google Scholar
  135. 135.
    Sander JWAS, Patsalos PN. An assessment of serum and red blood cell folate concentrations in patients with epilepsy on lamotrigine therapy. Epilepsy Res 1992; 13: 89–92PubMedGoogle Scholar
  136. 136.
    Gower AJ, Noyer M, Verloes R, et al. ucb L059, a novel anticonvulsant: pharmacological profile in animals. Eur J Pharmacol 1992; 222: 193–203PubMedGoogle Scholar
  137. 137.
    Loscher W, Honack D. Profile of ucb L059, a novel anticonvulsant drug, in models of partial and generalized epilepsy in mice and rats. Eur J Pharmacol 1993; 232: 147–58PubMedGoogle Scholar
  138. 138.
    Edelbroeck PM, de Wilde-Ockeleon JM, Kasteleijn-Nolst Trenite DGA, et al. Evaluation of the pharmacokinetics and neuropsychometric parameters in chronic comedicated epileptic patients of three increasing dosages of a novel, antiepileptic drug, ucb L059 250 mg capsules per each dose for one week followed by two weeks of placebo [abstract]. Epilepsia 1993; 34Suppl. 2: 7Google Scholar
  139. 139.
    Sharief MK, Singh P, Sander JWAS, et al. An efficacy and tolerability study of ucb L059 in patients with refractory epilepsy. Epilepsy Res. In pressGoogle Scholar
  140. 140.
    De Deyn PP, Bielen E, Saxena V, et al. Assessment of the safety of orally administered ucb L059 as add-on therapy in patients treated with antiepileptic drugs [abstract]. Seizure 1992; 1Suppl. A: P7/15Google Scholar
  141. 141.
    Singh P, Sharief MK, Sander JWAS, et al. A pilot study of the efficacy and tolerability of L059 in patients with refractory epilepsy [abstract]. Seizure 1992; 1Suppl. A: P7/46Google Scholar
  142. 142.
    Baltzer V, Schmutz M. Experimental anticonvulsive properties of GP 47680 and GP 47779, its main human metabolite, compounds related to carbamazepine. In: Mainardi H, Rowan AJ, editors. Advances in epileptology - 1977. Amsterdam: Swets and Zeitlinger, 1978: 295–9Google Scholar
  143. 143.
    Kubova H, Mares P. Anticonvulsant action of oxcarbazepine, hydroxy carbamazepine, and carbamazepine against metra-zol-induced seizures in developing rats. Epilepsia 1993; 34: 188–92PubMedGoogle Scholar
  144. 144.
    McLean MJ, Schmutz M, Wamil AM, et al. Oxcarbazepine: Mechanisms of action. Epilepsia 1994; 35(3 Suppl.): S5–9PubMedGoogle Scholar
  145. 145.
    Feldmann KF, Doerhoefer G, Faigle JW, et al. Pharmacokinetics and metabolism of GP4779, the main human metabolite of oxcarbazepine (GP47680) in animals and healthy volunteers. In: Dam M, Gram L, Penry JK, editors. Advances in epileptology. New York: Raven Press, 1981: 89–96Google Scholar
  146. 146.
    Kumps A, Wurth C. Oxcarbazepine disposition: preliminary observations in patients. Biopharm Drug Dispos 1990; 11: 365–70PubMedGoogle Scholar
  147. 147.
    Zakrzewska JM, Patsalos PN. Oxcarbazepine: a new drug in the management of intractable trigeminal neuralgia. J Neurol Neurosurg Psychiatry 1989; 52: 472–6PubMedGoogle Scholar
  148. 148.
    Dickinson G, Hooper WD, Dunstan PR, et al. First dose and steady-state pharmacokinetics of oxcarbazepine and its 10-hydroxy metabolite. Eur J Pharmacology 1989; 37: 69–74Google Scholar
  149. 149.
    Theisohn M, Heimann G. Disposition of the antiepileptic oxcarbazepine and its metabolites in healthy volunteers. Eur J Clin Pharmacol 1982; 22: 545–51PubMedGoogle Scholar
  150. 150.
    Van Heiningen PNM, Eve MD, Oosterhuis B, et al. The influence of age on the pharmacokinetics of the antiepileptic agent oxcarbazepine. Clin Pharmacol Ther 1991; 50: 410–9PubMedGoogle Scholar
  151. 151.
    Kristensen O, Klitgaard NA, Jonsson B, et al. Pharmacokinetics of 10-OH-carbazepine, the main metabolite of the antiepileptic oxcarbazepine, from serum and saliva concentrations. Acta Neurol Scand 1983; 68: 145–50PubMedGoogle Scholar
  152. 152.
    Klitgaard NA, Kristensen O. Use of saliva for monitoring oxcarbazepine therapy in epileptic patients. Eur J Clin Pharmacol 1986; 31: 91–4PubMedGoogle Scholar
  153. 153.
    Patsalos PN, Elyas AA, Zakrzewska JM. Protein binding of oxcarbazepine and its primary active metabolite, 10-hydroxycarbazepine, in patients with trigeminal neuralgia. Eur J Clin Pharmacol 1990; 39: 413–5PubMedGoogle Scholar
  154. 154.
    Faigle JW, Menge GP. Pharmacokinetic and metabolic features of oxcarbazepine and their clinical significance: comparison with carbamazepine. Int Clin Psychopharmacol 1990; 5Suppl. 1: 73–82Google Scholar
  155. 155.
    Abernethy DR, Greenblatt DJ, Ameer B, et al. Probenecid impairment of acetaminophen and lorazepam clearance: direct inhibition of ether glucuronidation. J Pharmacol Exp Ther 1985; 234: 345–9PubMedGoogle Scholar
  156. 156.
    Bock KW, Bock-Hennig BS. Differential induction of human liver UDP-glucuronosyl-transference activities by phenobarbital-type inducers. Biochem Pharmacol 1987; 36: 4137–43PubMedGoogle Scholar
  157. 157.
    Hirata M, Tonda K, Higaki J. Induction of 2-carboxybenzaldehyde reductase by phenobarbital in primary culture of rat hepatocytes. Biochem Biophys Res Commun 1986; 141: 488–93PubMedGoogle Scholar
  158. 158.
    Larkin JG, McKee PJW, Forrest G, et al. Lack of enzyme induction with oxcarbazepine (600mg daily) in healthy subjects. Br J Clin Pharmacol 1991; 31: 65–71PubMedGoogle Scholar
  159. 159.
    Patsalos PN, Zakrzewska JM, Elyas AA. Dose dependent enzyme induction by oxcarbazepine? Eur J Clin Pharmacol 1990; 39: 187–8PubMedGoogle Scholar
  160. 160.
    Arnoldussen W, Hulsman J, Rentmeester T. Interaction between oxcarbazepine and phenytoin [abstract]. Epilepsia 1993; 34Suppl. 6: 37Google Scholar
  161. 161.
    Tartara A, Galimberti CA, Manni R, et al. The pharmacokinetics of oxcarbazepine and its active metabolite 10-hydroxy-carbazepine in healthy subjects and in epileptic patients treated with phenobarbitone and valproic acid. Br J Clin Pharmacol 1993; 36: 366–8PubMedGoogle Scholar
  162. 162.
    McKee PJW, Blacklaw J, Forrest G, et al. A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients. Br J Clin Pharmacol 1994; 37: 27–32PubMedGoogle Scholar
  163. 163.
    Houtkooper MA, Lammertsma A, Meyer JWA, et al. Oxcarbazepine (GP 47.680): a possible alternate to carbamazepine? Epilepsia 1987; 28: 693–8PubMedGoogle Scholar
  164. 164.
    Keränen T, Jolkkonen J, Jensen PK, et al. Absence of interaction between oxcarbazepine and erythromycin. Acta Neurol Scand 1992; 86: 120–3PubMedGoogle Scholar
  165. 165.
    Keränen T, Jolkkonen J, Klosterskov-Jensen P, et al. Oxcarbazepine does not interact with cimetidine in healthy volunteers. Acta Neurol Scand 1992; 85: 239–42PubMedGoogle Scholar
  166. 166.
    Mogensen PH, Jørgensen L, Boas J, et al. Effect of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites. Acta Neurol Scand 1992; 853: 14–7Google Scholar
  167. 167.
    Krämer G, Tettenborn B, Klosterskov-Jensen P, et al. Oxcarbazepine does not affect the anticoagulant activity of warfarin. Epilepsia 1992; 33: 1145–8PubMedGoogle Scholar
  168. 168.
    Klosterskov-Jensen P, Saano V, Haring P, et al. Possible interaction between oxcarbazepine and an oral contraceptive. Epilepsia 1992; 33: 1149–52PubMedGoogle Scholar
  169. 169.
    Sonnen AEH. Oxcarbazepine and oral contraceptives [abstract]. Acta Neurol Scand 1990; 82Suppl. 133: 37Google Scholar
  170. 170.
    Dam M, Ekberg R, Loyning Y, et al. A double-blind study comparing oxcarbazepine and carbamazepine in patients with newly diagnosed previously untreated epilepsy. Epilepsy Res 1989; 3: 70–6PubMedGoogle Scholar
  171. 171.
    Reinikainen K, Kernen T, Hallibainen E, et al. Substitution of diphenylhydantoin by oxcarbazepine or carbamazepine: double-blind study. Acta Neurol Scand 1984; 69Suppl 98: 89–92Google Scholar
  172. 172.
    Dickinson RG, Hooper WD, Pendlebury SC, et al. Further clinical and pharmacokinetic observations on the new anticonvulsant, oxcarbazepine. Clin Exp Neurol 1988; 25: 127–33PubMedGoogle Scholar
  173. 173.
    Philbert A, Dam M, Jackobsen K. Oxcarbazepine in the treatment of epilepsy - a usable alternative to carbamazepine? [abstract]. Ir Neurol Assoc 1986; 155: 297Google Scholar
  174. 174.
    Sillanpaa M, Pihlaja T. Oxcarbazepine (GP47680) in the treatment of intractable seizures. Acta Paediatr Hung 1988–1989; 29: 359–61PubMedGoogle Scholar
  175. 175.
    Friis ML, Kristensen O, Boas J, et al. Therapeutic experiences with 947 epileptic out-patients in oxcarbazepine treatment. Acta Neurol Scand 1993; 87: 224–7PubMedGoogle Scholar
  176. 176.
    Gillham RA, Williams N, Wiedmann K, et al. Concentration-effect relationships with carbamazepine and its epoxide on psychomotor and cognitive function in epileptic patients. J Neurol Neurosurg Psychiatry 1988; 51: 929–33PubMedGoogle Scholar
  177. 177.
    Patsalos PN, Stephenson TJ, Krishna S, et al. Side-effects induced by carbamazepine-10,11-epoxide [letter]. Lancet 1985; 2: 496PubMedGoogle Scholar
  178. 178.
    Bulau P, Stoll KD, Froscher W. Oxcarbazepine versus carbamazepine. In: Wolf P, Dam M, Janz D, et al., editors. Advances in Epileptology, vol 16. New York: Raven Press, 1987; 531–6Google Scholar
  179. 179.
    Curran HV, Java R. Memory and psychomotor effects of oxcarbazepine in healthy human volunteers. Eur J Clin Pharmacol 1993; 44: 529–33PubMedGoogle Scholar
  180. 180.
    Äikiä M, Kalviainen R, Sivenius J, et al. Cognitive effects of oxcarbazepine and phenytoin monotherapy in newly diagnosed epilepsy: one year follow-up. Epilepsy Res 1992; 11: 199–203PubMedGoogle Scholar
  181. 181.
    Johannessen AC, Nielsen OA. Hyponatremia induced by oxcarbazepine. Epilepsy Res 1987; 1: 155–6PubMedGoogle Scholar
  182. 182.
    Nielson OA, Johannessen AC, Bardrum B. Oxcarbazepine-induced hyponatremia, a cross-sectional study. Epilepsy Res 1988; 2: 269–71Google Scholar
  183. 183.
    Pendlebury SC, Moses DK, Eadie MJ. Hyponatraemia during oxcarbazepine therapy. Hum Toxicol 1989; 8: 337–44PubMedGoogle Scholar
  184. 184.
    Steinhoff BJ, Stoll KD, Stodieck SRG, et al. Hyponatremic coma under oxcarbazepine therapy. Epilepsy Res 1992; 11: 67–70PubMedGoogle Scholar
  185. 185.
    Emrich HM. Studies with oxcarbazepine (Trileptal) in acute mania. Int Clin Psychopharmacol 1990; 5Suppl. 1: 83–8Google Scholar
  186. 186.
    Wildgrube C. Case studies on prophylactic long-term effects of oxcarbazepine in recurrent affective disorders. Int Clin Psychopharmacol 1990; 5Suppl 1: 89–94Google Scholar
  187. 187.
    Jensen NO, Dam M, Jackobsen K. Oxcarbazepine in patients hypersensitive to carbamazepine. Ir J Med Sci 1986; 155: 297Google Scholar
  188. 188.
    Beran R. Cross-reactive skin eruption with both carbamazepine and oxcarbazepine. Epilepsia 1993; 34: 163–5PubMedGoogle Scholar
  189. 189.
    Bulau P, Paar WD, von Unruh GE. Pharmacokinetics of oxcarbazepine and 10-hydroxy-carbazepine in the newborn child of an oxcarbazepine-treated mother. Eur J Clin Pharmacol 1988; 34: 311–3PubMedGoogle Scholar
  190. 190.
    Giurgea C, Moyersoon F, Evraerd AC. A GABA-related hypothesis on the mechanism of action of the antimotion-sickness drugs. Arch Int Pharmacodyn Ther 1967; 166: 238–51PubMedGoogle Scholar
  191. 191.
    Vial H, Claustre Y, Pacheco H. Effects de substances stimulantes, sedatives et hypnotiques sur le taux d’aminoacides cerebrales libres chez le rat. J Pharmacol 1974; 5: 461–78Google Scholar
  192. 192.
    Nyback H, Wiesel FA, Skett P. Effects of piracetam on brain monoamine metabolism and serum prolactin levels in the rat. Psychopharmacology 1979; 61: 235–8PubMedGoogle Scholar
  193. 193.
    Rago LK, Allikonets LH, Zarkowsky AM. Effect of piracetam on central dopaminergic transmission. Naunyn Schmiederbergs Arch Pharm Pathol 1981; 318: 36–7Google Scholar
  194. 194.
    Valzelli L, Barnasconi S, Sala A. Piracetam activity may differ according to the age of the recipient mouse. Int J Pharmacopsychiatry 1980; 15: 150–6Google Scholar
  195. 195.
    Piercey MF, Vogelsang GD, Franklin SR, et al. Reversal of scopolamine-induced amnesia and alterations in energy metabolism by the nootropic piracetam: implications regarding identification of brain structures involved in consolidation of memory traces. Brain Res 1987; 424: 1–9PubMedGoogle Scholar
  196. 196.
    Bartus RT, Dean RL, Sherman KA, et al. Profound effect of combining choline and piracetam in memory enhancement and cholinergic functions in aged rats. Neurobiol Aging 1981; 2: 105–11PubMedGoogle Scholar
  197. 197.
    Stoll L, Schubert T, Muller WE. Age-related deficits of central muscurinic cholinergic receptor function in the mouse: partial restoration by chronic piracetam treatment. Neurobiol Aging 1991; 13: 39–44Google Scholar
  198. 198.
    Wurtman RJ, Magill SG, Reinstein SK. Piracetam diminishes hippocampal acetylcholine levels in rats. Life Sci 1981; 28: 1091–3PubMedGoogle Scholar
  199. 199.
    Bering B, Muller WE. Interaction of piracetam with several neurotransmitter receptors in the central nervous system. Relative specificity of 3H-glutamate sites. Arzneimittelforschung 1985; 35: 1350–2PubMedGoogle Scholar
  200. 200.
    Copani A, Genazzani AA, Aleppo G, et al. Nootropic drugs positively modulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid sensitive glutamate receptors in neuronal cultures. J Neurochem 1992; 58: 1199–204PubMedGoogle Scholar
  201. 201.
    Cohen SH, Muller WE. Effects of piracetam on N-methyl-Daspartate receptor properties in the aged mouse brain. Pharmacology 1993; 47: 217–22PubMedGoogle Scholar
  202. 202.
    Mondadori C, Bhatnager A, Bortkowski J, et al. Involvement of a steroidal component in the mechanism of action of piracetam-like nootropics. Brain Res 1990; 506: 101–8PubMedGoogle Scholar
  203. 203.
    Morgenstern E, Stattman A, Voig JR Influence of piracetam on anticonvulsant effects of antiepileptic drugs in mice. Activ Nerv Super 1990; 32: 55–6Google Scholar
  204. 204.
    Moyersoons FE, Evraerd A, Dauby J, et al. A particular pharmacological effect on the propagation of experimental strychnine and penicillin epilepsy. Arch Int Pharmacodyn Ther 1969; 179: 388–400PubMedGoogle Scholar
  205. 205.
    Gobert JG. Availability and plasma clearance of piracetam in man. II Farmaco 1977; 32: 84–91Google Scholar
  206. 206.
    Gobert JG. Genese d’un medicament: Le piracetam. Metabolisation et recherche biochimique. J Pharm Belg 1972; 27: 281–304Google Scholar
  207. 207.
    Ostrowski J, Keil M, Schraven E. Autoradiographische Untersuchungen zur Verteilung von Piracetam 1 C bei Ratte und Hund. Arzneimittelforschung 1975; 25: 589–96PubMedGoogle Scholar
  208. 208.
    Tacconi MT, Wurtman R. Piracetam: physiological disposition and mechanism of action. In: Fahn S, Marsden CD, Van Woert M, editors. Advances in neurology, Vol 43 Myoclonus. New York: Raven Press, 1986: 675–85Google Scholar
  209. 209.
    Barnas C, Miller C, Ehrmann H, et al. High versus low-dose piracetam in alcohol organic mental disorder: a placebo controlled study. Psychopharmacology 1990; 100: 361–5PubMedGoogle Scholar
  210. 210.
    Carrington Da Costa RB, Maul ER, Pimental J, et al. A controlled clinical study of piracetam v placebo in disorders of consciousness due to head injuries. Acta Ther 1978; 4: 109–18Google Scholar
  211. 211.
    Chouinard G, Annable L, Roso-Chouinard A, et al. Piracetam in elderly psychiatric patients with mild diffuse cerebral impairment. Psychopharmacol Bull 1983; 81: 100–6Google Scholar
  212. 212.
    Croisile B, Trillet M, Fondarai J, et al. Long-term high-dose piracetam treatment of Alzheimer’s disease. Neurology 1993; 43: 301–5PubMedGoogle Scholar
  213. 213.
    Kunneke PJ, Malan GM. A controlled clinical trial on the effect of piracetam in epileptic children. Br J Clin Pract 1979; 33: 226–71Google Scholar
  214. 214.
    Richardson AE, Bereen FJ. Effect of piracetam on level of consciousness after neurosurgery. Lancet 1977; 2: 1110–1PubMedGoogle Scholar
  215. 215.
    Sano M, Stern Y, Marder K, et al. A controlled trial of piracetam in intellectually impaired patients with Parkinson’s Disease. Mov Disord 1990; 5: 230–4PubMedGoogle Scholar
  216. 216.
    Wilsher CR, Bennet D, Chase H, et al. Piracetam and dyslexia: effects on reading tests. J Clin Psychopharmacol 1987; 7: 230–7PubMedGoogle Scholar
  217. 217.
    Helfgott E, Rudel RG, Kairam R. The effect of piracetam on short- and long-term verbal retrieval in dyslexic boys. Int J Psychophysiol 1986; 4: 53–61PubMedGoogle Scholar
  218. 218.
    Tallal P, Chase CH, Russell G, et al. Evaluation of the efficacy of piracetam in treating information processing, reading and writing disorders in dyslexic children. Int J Psychophysiol 1986; 4: 41–52PubMedGoogle Scholar
  219. 219.
    Terwinghe G, Daumerie J, Nicaise C, et al. Effet therapeutique du piracetam dans un cas de myoclonies d’action post-anoxique. Acta Neurol Belg 1978; 78: 30–6PubMedGoogle Scholar
  220. 220.
    Cremieux C, Serratrice G. Myoclonies d’intention et d’action postanoxiques: amélioration par le piracetam. Nouveux Press Med 1979; 41: 3357–8Google Scholar
  221. 221.
    Fahn S. New drugs for posthypoxic action myoclonus: observations from a well studied case. Adv Neurol 1986; 43: 197–9PubMedGoogle Scholar
  222. 222.
    Papyrakis JC. Management of a case of myoclonia. Acta Ther 1987; 13: 109–14Google Scholar
  223. 223.
    Obeso JA, Artieda J, Luquin MR, et al. Antimyoclonic action of piracetam. Clin Neuropharmacol 1986; 9: 58–64PubMedGoogle Scholar
  224. 224.
    Obeso JA, Artieda J, Quinn N, et al. Piracetam in the treatment of different types of myoclonus. Clin Neuropharmacol 1988; 11: 529–36PubMedGoogle Scholar
  225. 225.
    Brown P, Steiger MJ, Thompson PD, et al. Effectiveness of piracetam in cortical myoclonus. Mov Disord 1993; 8: 63–8PubMedGoogle Scholar
  226. 226.
    Dzabac A, Kresci I, Kupkova B. The interaction of nootropic drugs with anticonvulsants. Activ Nerv Sup 1981; 2313: 218–9Google Scholar
  227. 227.
    Hawkins CA, Mellanby JH. Piracetam potentiates the anti-epileptic action of carbamazepine in chronic experimental limbic epilepsy. Acta Neurol Scand 1986; 74Suppl. 109: 117–21Google Scholar
  228. 228.
    Mondadori C, Schmutz M. Synergistic effects of oxiracetam and piracetam in combination with anti-epileptic drugs. Acta Neurol Scand 1986; 74Suppl. 109: 113–8Google Scholar
  229. 229.
    Mondadori C, Schmutz M, Baltzer V. Potentiation of the anticonvulsant effects of anti-epileptic drugs by ‘nootropics’, a potential new therapeutic approach. Acta Neurol Scand 1984; 69Suppl. 99: 131–2Google Scholar
  230. 230.
    Chaudhry HR, Najam N, De Mahieu C, et al. Clinical use of piracetam in epileptic patients. Curr Ther Res 1992; 52: 355–60Google Scholar
  231. 231.
    Palmer GC, Harris EW, Napier JJ, et al. Status of PR 934-423, a new anticonvulsant targeted for generalized tonic-clonic seizures. In: Williams M, editor. Current and future trends in anticonvulsant, anxiety and stroke therapy. New York: Wiley-Liss, 1992: 435–42Google Scholar
  232. 232.
    Palmer GC, Murray RJ, Wilson TCM, et al. Biological profile of the metabolites and the potential metabolites of the anticonvulsant remacemide. Epilepsy Res 1992; 12: 9–20PubMedGoogle Scholar
  233. 233.
    Garske GE, Palmer GC, Napier JJ, et al. Preclinical profile of the anticonvulsant remacemide and its enantiomers in the rat. Epilepsy Res 1991; 9: 161–74PubMedGoogle Scholar
  234. 234.
    Stagnitto ML, Palmer GC, Ordy JM, et al. Preclinical profile of remacemide: a novel anticonvulsant effective against maximal electroshock seizures in mice. Epilepsy Res 1990; 7: 11–28PubMedGoogle Scholar
  235. 235.
    Palmer GC, Stagnitto ML, Ordy JM, et al. Preclinical profile of stereoisomers of the anticonvulsant remacemide in mice. Epilepsy Res 1991; 8: 36–48PubMedGoogle Scholar
  236. 236.
    Muir KT, Palmer GC. Remacemide. In: Pisani F, Perucca E, Arazini G, et al., editors. New antiepileptic drugs. Epilepsy Research Suppl. 3. Amsterdam: Elsevier Science Publishers, 1991: 147–52Google Scholar
  237. 237.
    Scheyer RD, Cramer JA, Leppik IE, et al. Remacemide elimination after initial and chronic dosing [abstract]. Clin Pharmacol Ther 1992; 51: 189Google Scholar
  238. 238.
    Alarcon G, Binnie CD, Elwes RDC, et al. Remacemide monotherapy in patients undergoing acute anti-epileptic drug withdrawal [abstract]. Seizure 1992; 1Suppl. A: P7/01Google Scholar
  239. 239.
    Crawford P, Richens A, Mower G, et al. A double-blind placebo controlled cross-over study of remacemide hydrochloride as adjunctive therapy in patients with refractory epilepsy [abstract]. Seizure 1992; Suppl. A: P7/13Google Scholar
  240. 240.
    Owen L, Cresswell P, Gifford C, et al. Influence of remacemide on EEG in chronic epilepsy [abstract]. Seizure 1992; 1Suppl. A: P7/32Google Scholar
  241. 241.
    Lockard JS, Levy RH, Rhodes PH, et al. Stiripentol in acute/chronic efficacy tests in monkey model. Epilepsia 1985; 26: 704–12PubMedGoogle Scholar
  242. 242.
    Poisson M, Hugnet F, Savattier A, et al. A new type of anticonvulsant, stiripentol. Arzneimittelforschung 1984; 34: 199–204PubMedGoogle Scholar
  243. 243.
    Shen DD, Levy RH, Moor MJ, et al. Efficacy of stiripentol in the intravenous pentylenetetrazol infusion seizure model in the rat. Epilepsy Res 1990; 7: 40–8PubMedGoogle Scholar
  244. 244.
    Vincent JC. Stiripentol. In: Pisani F, Perucca E, Arazini G, editors. New antiepileptic drugs. Epilepsy Research Suppl. 3. Amsterdam: Elsevier Science Publishers, 1991: 153–8Google Scholar
  245. 245.
    Wegmann R, Ilies A, Aurousseau M. Pharmaco-cellular enzymology of the mode of action of the stiripentol during the cardiozolic epilepsy. III. The metabolism of lipids, proteins, nucleoproteins and proteoglycans. Cell Mol Biol 1978; 23: 455–80Google Scholar
  246. 246.
    Levy RH, Lin HS, Blehaut HM, et al. Pharmacokinetics of stiripentol in normal man: evidence of nonlinearity. J Clin Pharmacol 1983; 23: 523–33PubMedGoogle Scholar
  247. 247.
    Lin HJ, Levy RH, Pharmacokinetic profile of a new anticonvulsant, stiripentol, in the rhesus monkey. Epilepsia 1983; 24: 692–702PubMedGoogle Scholar
  248. 248.
    Levy RH, Loiseau P, Guyot M, et al. Stiripentol kinetics in epilepsy: nonlinearity and interactions. Clin Pharmacol Ther 1984; 36: 661–9PubMedGoogle Scholar
  249. 249.
    Levy RH, Loiseau P, Guyot M, et al. Michaelis-Menten kinetics of stiripentol in normal humans. Epilepsia 1984; 25: 486–91PubMedGoogle Scholar
  250. 250.
    Martinez-Lage JM, Loiseau P, Levy RH, et al. Clinical antiepileptic efficacy of stiripentol in resistant partial epilepsies [abstract]. Epilepsia 1984; 25: 673Google Scholar
  251. 251.
    Rascol O, Squalli A, Montastruc JL, et al. A pilot study of stiripentol, a new anticonvulsant drug, in complex partial seizures uncontrolled by carbamazepine. Clin Neuropharmacol 1989; 12: 119–23PubMedGoogle Scholar
  252. 252.
    Kerr BM, Martinez-Lage JM, Viteri C, et al. Carbamazepine dose requirements during stiripentol therapy: influence of cytochrome P450 inhibition by stiripentol. Epilepsia 1991; 32: 267–74PubMedGoogle Scholar
  253. 253.
    Levy RH, Kerr BM, Farwell J, et al. Carbamazepine/stiripentol interaction in adult and pediatric patients [abstract]. Epilepsia 1989; 30: 701Google Scholar
  254. 254.
    Lockard JS, Levy RH. Carbamazepine plus stiripentol: is polytherapy by design possible? Epilepsia 1988; 29: 476–81PubMedGoogle Scholar
  255. 255.
    Mesnil M, Testa B, Jenner P. In vitro inhibition by stiripentol of rat brain cytochrome P450-mediated naphthalene hydroxylation. Xenobiotica 1988; 18: 1097–106PubMedGoogle Scholar
  256. 256.
    Levy RH, Rettenmeir AW, Anderson GD, et al. Effects of polytherapy with phenytoin, carbamazepine and stiripentol in formation of 4-ene-valproate, a hepatotoxic metabolite of valproic acid. Clin Pharmacol Ther 1990; 48: 225–35PubMedGoogle Scholar
  257. 257.
    Loiseau P, Duche B. Potential antiepileptic drugs: stiripentol. In: Levy R, Mattson R, Meldrum B, et al., editors. Antiepileptic drugs, 3rd ed. New York: Raven Press, 1989: 955–69Google Scholar
  258. 258.
    Farwell JR, Anderson GD, Kerr BM, et al. Stiripentol in atypical absence seizures in children: an open trial. Epilepsia 1993; 34: 305–110PubMedGoogle Scholar
  259. 259.
    Loiseau P, Strube E, Tor J, et al. Evaluation neuropsychologique et therapeutique du stiripentol dans l’epilepsie. Resultats preliminaires. Rev Neurol Paris 1988; 144: 165–72PubMedGoogle Scholar
  260. 260.
    Braestrup C, Nielsen EB, Sonnewald U, et al. (R)-N[4.4-bis(3-methyl-2-thienyl)but-3-en-l-yl] nipecotic acid binds with high affinity to the brain γ-aminobutyric acid uptake carrier. J Neurochem 1990; 54: 634–47Google Scholar
  261. 261.
    Fink-Jensen A, Suzdak PD, Swedberg MDB, et al. The yaminobutyric acid (GABA) uptake inhibitor, tiagabine, increases extracellular brain levels of GABA in awake rats. Eur J Pharmacol 1992; 220: 197–201PubMedGoogle Scholar
  262. 262.
    Roepstorff A, Lambert JDC. Comparison of the effect of the GABA uptake blockers, tiagabine and nipecotic acid, on inhibitory synaptic efficacy in hippocampal CA1 neurons. Neurosci Lett 1992; 146: 131–4PubMedGoogle Scholar
  263. 263.
    Nielsen EB, Suzdak PD, Andersen KE, et al. Characterization of tiagabine (NO-328), a new potent selective GABA uptake inhibitor. Eur J Pharmacol 1991; 196: 257–66PubMedGoogle Scholar
  264. 264.
    Pierce MW, Suzdak PD, Gustavson LE, et al. Tiagabine. In: Pisani F, Perucca E, Avanzini G, et al. editors. New antiepileptic drugs. Epilepsy Res Suppl. 3. Amsterdam: Elsevier Science Publishers, 1991: 157–60Google Scholar
  265. 265.
    Mengel HB, Pierce MW, Mant TGB, et al. Tiagabine: safety and tolerance during 2-weeks multiple dosing to healthy volunteers [abstract]. Epilepsia 1991; 32Suppl 1: 99–100Google Scholar
  266. 266.
    Bopp BA, Gustavson LE, Johnson MK, et al. Disposition and metabolism of orally administered 14C-tiagabine in humans [abstract]. Epilepsia 1992; 33(3 Suppl.): 83Google Scholar
  267. 267.
    Gustavson LE, Mengel HB, Pierce MW, et al. Tiagabine, a new γ-aminobutyric acid uptake inhibitor antiepileptic drug: pharmacokinetics after single oral doses in man [abstract]. Epilepsia 1990; 31: 642Google Scholar
  268. 268.
    Richens A, Gustavson LE, McKelvy JF, et al. Pharmacokinetics and safety of single-dose tiagabine HCL in epileptic patients chronically treated with four other antiepileptic drug regimens [abstract]. Epilepsia 1991; 32Suppl. 1: 12Google Scholar
  269. 269.
    Leppik IE, So E, Pask CA, et al. Pharmacokinetic study of tiagabine HCL in patients at multiple steady state dose [abstract]. Epilepsia 1993; 34Suppl. 6: 35Google Scholar
  270. 270.
    Cahill WT, Sachdeo RC, Schachter S, et al. Dose ranging study to determine the safety and tolerability of tiagabine HCL administered as monotherapy [abstract]. Epilepsia 1993; 34Suppl. 6: 36Google Scholar
  271. 271.
    Crawford PM, Engelsman M, Brown SW, et al. Tiagabine: Phase II study of efficacy and safety in adjunctive treatment of partial seizures [abstract]. Epilepsia 1993; 34(2 Suppl.): 182Google Scholar
  272. 272.
    Sachdeo RC, Leroy R, Green P, et al. Safety and efficacy of b.i.d. and q.i.d. dosing with tiagabine HCL versus placebo as adjunctive treatment for partial seizures [abstract]. Epilepsia 1993; 34Suppl. 6: 36Google Scholar
  273. 273.
    Sveinbjornsdottir S, Sander JWAS, Patsalos PN, et al. Neuropsychological effects of tiagabine, a potential new antiepileptic drug. Seizure 1994; 3: 29–35PubMedGoogle Scholar
  274. 274.
    Richens A, Chadwick D, Duncan J, et al. Safety and efficacy of tiagabine HCL as adjunctive treatment for complex partial seizures [abstract]. Epilepsia 1992; 33Suppl. 3: 119Google Scholar
  275. 275.
    Rowan J, Ahmann P, Wannamaker B, et al. Safety and efficacy of three doses of tiagabine HCL versus placebo as adjunctive treatment for complex partial seizures [abstract]. Epilepsia 1993; 34Suppl. 2: 157Google Scholar
  276. 276.
    Mengel HB, Mant TGK, McKelvy JM, et al. Tiagabine: phase I study of safety and tolerance following single oral doses. Epilepsia 1990; 31: 642–3Google Scholar
  277. 277.
    Maryanoff BE, Nortey SO, Gardocki JF, et al. Anticonvulsant O-alkyl sulfamates. 2,3:4,5-Bis-0-(1-methylidene) B-D-fractopyranose sulfamate and related compounds. J Med Chem 1987; 30: 880–7PubMedGoogle Scholar
  278. 278.
    Shank RP, Gardocki JF, Vaught JL, et al. Topiramate: preclinical evaluation of a structurally novel anticonvulsant. Epilepsia 1994; 35: 450–60PubMedGoogle Scholar
  279. 279.
    Brown SD, Wolf HH, Swinyard EA, et al. The novel anticonvulsant topiramate enhances GABA-mediated chloride flux [abstract]. Epilepsia 1993; 34(2 Suppl.): 122–3Google Scholar
  280. 280.
    Bialer M. Comparative pharmacokinetics of the newer antiepileptic drugs. Clin Pharmacokinet 1993; 24: 441–52PubMedGoogle Scholar
  281. 281.
    Floren KL, Graves NM, Leppik IE, et al. Pharmacokinetics of topiramate in patients with partial epilepsy receiving phenytoin or valproic acid [abstract]. Epilepsia 1989; 30: 646Google Scholar
  282. 282.
    Wilensky AJ, Ojemann LM, Chmelir T, et al. Topiramate pharmacokinetics in epileptic patients receiving carbamazepine [abstract]. Epilepsia 1989; 30: 645–6Google Scholar
  283. 283.
    Levy RH. The clinical pharmacokinetics of topiramate. In: Topiramate a promising new agent for the treatment of epilepsy. Symposium at the 20th International Epilepsy Congress; 1993 July 4: NorwayGoogle Scholar
  284. 284.
    Engelskjon T, Johannessen SI, Kloster R, et al. Topiramate in the treatment of refractory partial epilepsy - an efficacy and tolerance study [abstract]. Seizure 1992; 1Suppl. A: P7/KGoogle Scholar
  285. 285.
    Mikkelsen M, Dam M, Ostergaard L. Topiramate as add-on therapy in refractory partial seizures [abstract]. Seizure 1992; 1Suppl. A: P7/31Google Scholar
  286. 286.
    Sharief K, Sander JWAS, Patsalos PN, et al. Double blind parallel comparison of topiramate with placebo in patients with refractory partial epilepsy [abstract]. Seizure 1992; 1Suppl.A: P7/45Google Scholar
  287. 287.
    Sharief MK, Sander JWAS, Shorvon SD. Long-term treatment with topiramate in refractory partial epilepsy. A two-year follow-up study [abstract]. Seizure 1992; 1Suppl.A: P7/47Google Scholar
  288. 288.
    Sharief MK, Sander JWAS, Patsalos PN, et al. Adjuvant topiramate treatment in intractable partial epilepsy [abstract]. Epilepsia 1993; 34Suppl. 6: 41Google Scholar
  289. 289.
    Lippert B, Metcalf BW, Jung MJ, et al. 4-Amino-hex-5-enoic acid, a selective catalytic inhibitor of 4-aminobutyric-acid aminotransferase in mammalian brain. Eur J Biochem 1977; 74: 441–5PubMedGoogle Scholar
  290. 290.
    Larsson OM, Gram L, Schousboe I, et al. Differential effect of gamma-vinyl GABA and valproate on GABA-transaminase from cultured neurons and astrocytes. Neuropharmacol 1986; 25: 617–25Google Scholar
  291. 291.
    Ben-Menachem E. Pharmacokinetic effects of vigabatrin on cerebrospinal fluid amino acids in humans. Epilepsia 1989; 30Suppl. 3: S12–4PubMedGoogle Scholar
  292. 292.
    Grove J, Schechter PJ, Tell G, et al. Increased gamma-aminobutyric acid (GABA), homocarnosine and β-alanine in cerebrospinal fluid of patients treated with γ-vinyl GABA (4-amino-hex-5-enoic acid). Life Sci 1981; 28: 2431–9PubMedGoogle Scholar
  293. 293.
    Halonen T, Lehtinen M, Pitkanen A, et al. Inhibitory and excitatory amino acids in CSF of patients suffering from complex partial seizures during chronic treatment with γ-vinyl GABA (vigabatrin). Epilepsy Res 1988; 2: 246–52PubMedGoogle Scholar
  294. 294.
    Loscher W. Effect of inhibitors of GABA aminotransferase on the metabolism of GABA in brain tissue and synaptosomal fractions. J Neurochem 1981; 36: 1521–7PubMedGoogle Scholar
  295. 295.
    Preece NE, Jackson GD, Houseman JA, et al. Nuclear magnetic resonance detection of increased cortical GABA in vigabatrin-treated rats in vivo. Epilepsia 1994; 35: 431–6PubMedGoogle Scholar
  296. 296.
    Riekkinen PJ, Pitkanen A, Ylinen A, et al. Specificity of vigabatrin for the GABAergic system in human epilepsy. Epilepsia 1989; 30Suppl. 3: S18–22PubMedGoogle Scholar
  297. 297.
    Sarhan S, Seiler N. Metabolic inhibitors and subcellular distribution of GABA. J Neurosci Res 1979; 4: 399–421PubMedGoogle Scholar
  298. 298.
    Bernasconi R, Klein M, Martin P, et al. γ-Vinyl GABA: a comparison of neurochemical and anticonvulsant effects in mice. J Neural Transm 1988; 72: 213–33PubMedGoogle Scholar
  299. 299.
    Liu Z, Seiler N, Mareseaux C, et al. Potentiation of γ-vinyl GABA (vigabatrin) effects by glycine. Eur J Pharmacol 1990; 182: 109–15PubMedGoogle Scholar
  300. 300.
    Meldrum B, Horton R. Blockade of epileptic response in the photosensitive baboon, Papio papio, by two irreversible inhibitors of GABA-transaminase, γ-acetylenic GABA (4 amino-hex-5 ynoic acid) and γ-vinyl GABA (4 amino-hex-5-enoic acid). Psychopharmacology 1978; 59: 47–50PubMedGoogle Scholar
  301. 301.
    Loscher W, Frey HH. One to three day dose intervals during subchronic treatment of epileptic gerbils with γ-vinyl GABA: anticonvulsant efficacy and alterations in regional brain GABA levels. Eur J Pharmacol 1987; 143: 335–42PubMedGoogle Scholar
  302. 302.
    Frisk-Holmberg M, Kerth P, Meyer PL. Effect of food on the absorption of vigabatrin. Br J Clin Pharmacol 1989; 27: 235–55Google Scholar
  303. 303.
    Haegele KD, Schechter PJ. Kinetics of the enantiomers of vigabatrin after an oral dose of the racemate or the active S-enantiomer. Clin Pharmacol Ther 1986; 40: 581–5PubMedGoogle Scholar
  304. 304.
    Hoke JF, Chi EM, Antony KK, et al. Bioequivalence and relative bioavailability of vigabatrin. Epilepsia 1991; 32Suppl. 3: 7Google Scholar
  305. 305.
    Grove J, Aiken RG, Schechter PJ. Assay of gamma-vinyl-gamma-aminobutyric acid (4-amino-hex-5-enoic acid) in plasma and urine by automatic amino acid analysis. J Chromatogr 1984; 306: 383–7PubMedGoogle Scholar
  306. 306.
    Durham SL, Hoke JF, Chen TM. Pharmacokinetics and metabolism of vigabatrin following a single oral dose of [14C] vigabatrin in healthy male volunteers. Drug Metab Dispos 1993; 21: 480–4PubMedGoogle Scholar
  307. 307.
    Rimmer EM, Richens A. Interaction between vigabatrin and phenytoin. Br J Clin Pharmacol 1989; 27: 27S–33SPubMedGoogle Scholar
  308. 308.
    Hoke JF, Yuh L, Antony KK, et al. Pharmacokinetics of vigabatrin following single and multiple oral doses in normal volunteers. J Clin Pharmacol 1993; 33: 458–62PubMedGoogle Scholar
  309. 309.
    Saletu B, Grunberger J, Linzmayer L, et al. Psychophysiological and psychometric studies after manipulating the GABA system by vigabatrin, a GABA-transaminase inhibitor. Int J Psychophysiol 1986; 4: 63–80PubMedGoogle Scholar
  310. 310.
    Ben-Menachem E, Persson LI, Schechter PJ, et al. Effects of single doses of vigabatrin on CSF concentrations of GABA, homocarnosine, homovanillic acid and 5-hydroxyindoleacetic acid in patients with complex partial epilepsy. Epilepsy Res 1988; 2: 96–101Google Scholar
  311. 311.
    Browne TR, Mattson RH, Penry JK, et al. Vigabatrin for refractory complex partial seizures: multicenter single blind study with long-term follow-up. Neurology 1987; 37: 184–9PubMedGoogle Scholar
  312. 312.
    Rimmer E, Kongola G, Richens A. Inhibition of the enzyme, GABA-aminotransferase in human platelets by vigabatrin, a potential antiepileptic drug. Br J Clin Pharmacol 1988; 25: 251–9PubMedGoogle Scholar
  313. 313.
    Szylleyko OJ, Hoke JF, Eller MG, et al. A definitive study evaluating the pharmacokinetics of vigabatrin in patients with epilepsy [abstract]. Epilepsia 1993; 34Suppl. 6: 41–2Google Scholar
  314. 314.
    Hutcheson S, Yu DK, Szylleyko O, et al. Pharmacokinetics of vigabatrin in patients with varying degrees of renal function [abstract]. Epilepsia 1993; 34Suppl. 6: 106Google Scholar
  315. 315.
    Besser R, Kramer G, Thumle R. Vigabatrin bei therapieresistenen Epilepsien. Aktuel Neurologie 1989; 16: 79–83Google Scholar
  316. 316.
    Cocito L, Maffini M, Perfumo P, et al. Vigabatrin in complex partial seizures: a long-term study. Epilepsy Res 1989; 3: 160–6PubMedGoogle Scholar
  317. 317.
    Luna D, Dulac O, Pujot N, et al. Vigabatrin in the treatment of childhood epilepsies: a single-blind placebo-controlled study. Epilepsia 1989; 30: 430–7PubMedGoogle Scholar
  318. 318.
    Rimmer EM, Richens A. Double-blind study of γ-vinyl GABA in patients with refractory epilepsy. Lancet 1984; 1: 189–90PubMedGoogle Scholar
  319. 319.
    Tartara A, Manni R, Galimberti CA, et al. Vigabatrin in the treatment of epilepsy: a long-term follow-up study. J Neurol Neurosurg Psychiatry 1989; 52: 467–71PubMedGoogle Scholar
  320. 320.
    Gatti G, Bartoli A, Marchiselli R, et al. Vigabatrin-induced decrease in serum phenytoin concentration does not involve a change in phenytoin bioavailability. Br J Clin Pharmacol 1993; 36: 603–5PubMedGoogle Scholar
  321. 321.
    Al-Hassan MI, Bawazir SA, Al-Khamis KI, et al. The interaction potential of vigabatrin with phenytoin and carbamazepine. Int J Pharmacokinet 1993; 93: 7–12Google Scholar
  322. 322.
    Dam M. Long-term evaluation of vigabatrin (gamma vinyl GABA) in epilepsy. Epilepsia 1989; 30Suppl. 3: S28–30Google Scholar
  323. 323.
    Gram L, Klosterskov P, Dan M. γ-Vinyl GABA: a double-blind placebo-controlled trial in partial epilepsy. Ann Neurol 1985; 17: 262–6PubMedGoogle Scholar
  324. 324.
    Grunewald RA, Thompson PJ, Corcoran R, et al. Effects of vigabatrin on partial seizures and cognitive function. J Neurol Neurosurg Psychiatry. In pressGoogle Scholar
  325. 325.
    Loiseau P, Hardenberg JP, Pestre M, et al. Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug resistant epilepsy. Epilepsia 1986; 27: 115–20PubMedGoogle Scholar
  326. 326.
    Martin PJ, Millac PAH. Vigabatrin: a three year clinical analysis. Seizure 1993; 2: 137–40PubMedGoogle Scholar
  327. 327.
    Matilainen R, Pitkanen A, Ruutiainen T, et al. Effect of vigabatrin on epilepsy in mentally retarded patients: a 7 month follow up study. Neurology 1988; 38: 743–7PubMedGoogle Scholar
  328. 328.
    Pedersen SA, Klosterskov P, Gram L, et al. Long-term study of gamma-vinyl GABA in the treatment of epilepsy. Acta Neurol Scand 1985; 72: 295–8PubMedGoogle Scholar
  329. 329.
    Remy C, Beaumont D. Efficacy and safety of vigabatrin in the long-term treatment of refractory epilepsy. Br J Clin Pharmacol 1989; 27: 125S–9SPubMedGoogle Scholar
  330. 330.
    Reynolds EH, Ring HA, Farr IN, et al. Open, double-blind and long term study of vigabatrin in chronic epilepsy. Epilepsia 1991; 32: 530–8PubMedGoogle Scholar
  331. 331.
    Ring HA, Heller AJ, Farr IN, et al. Vigabatrin: rational treatment for chronic epilepsy. J Neurol Neurosurg Psychiatry 1990; 53: 1051–5PubMedGoogle Scholar
  332. 332.
    Sander JWAS, Trevisol-Bitterscourt PC, Hart YM, et al. Evaluation of vigabatrin as an add-on drug in the management of severe epilepsy. J Neurol Neurosurg Psychiatry 1990; 53: 1008–10PubMedGoogle Scholar
  333. 333.
    Tartara A, Manni R, Galimberti CA, et al. Vigabatrin in the treatment of epilepsy: a double-blind, placebo-controlled study. Epilepsia 1986; 27: 717–23PubMedGoogle Scholar
  334. 334.
    Tartara A, Manni R, Galimberti CA, et al. Six-year follow-up study on the efficacy and safety of vigabatrin in patients with epilepsy. Acta Neurol Scand 1992; 86: 247–51PubMedGoogle Scholar
  335. 335.
    Tassinari CA, Michelucci R, Ambrosetto G, et al. Double-blind study of vigabatrin in the treatment of drug-resistant epilepsy. Arch Neurol 1987; 44: 907–10PubMedGoogle Scholar
  336. 336.
    Michelucci R, Tassinari CA. Response to vigabatrin in relation to seizure type. Br J Clin Pharmacol 1989; 27: 119S–24SPubMedGoogle Scholar
  337. 337.
    Mumford JP, Dam M. Meta-analysis of European placebo controlled studies of vigabatrin in drug resistant epilepsy. Br J Clin Pharmacol 1989; 27: 101S–7SPubMedGoogle Scholar
  338. 338.
    Kalviainen R, Halonen T, Pitkanen A, et al. Amino acid levels in the cerebrospinal fluid of newly diagnosed epileptic patients: effect of vigabatrin and carbamazepine monotherapies. J Neurochem 1993; 60: 1244–50PubMedGoogle Scholar
  339. 339.
    Sivenius MRJ, Ylinen A, Murros K, et al. Vigabatrin in drug-resistant partial epilepsy: a 5-year follow-up study. Neurology 1991; 41: 562–5PubMedGoogle Scholar
  340. 340.
    Ylinen A, Sivenius J, Pitkanen A, et al. γ-Vinyl GABA (vigabatrin) in epilepsy: clinical, neurochemical, and neurophysiologic monitoring in epileptic patients. Epilepsia 1992; 35: 917–22Google Scholar
  341. 341.
    Chiron L, Dulac O, Luna D, et al. Vigabatrin in infantile spasms. Lancet 1990; 10: 363–4Google Scholar
  342. 342.
    Vies JSH, van der Heyden AMHG, Ghijs A, et al. Vigabatrin in the treatment of infantile spasms. Neuropediatrics 1993; 24: 230–1Google Scholar
  343. 343.
    Arzimanoglou A, Aicardi J. The epilepsy of Sturge Weber syndrome: clinical features and treatment in 23 patients. Acta Neurol Scand 1992; 88Suppl. 140: 18–22Google Scholar
  344. 344.
    Buchanan N, Kearney B. Vigabatrin in the Sturge Weber syndrome. Med J Aust 1993; 158: 652PubMedGoogle Scholar
  345. 345.
    Appleton RE. The role of vigabatrin in the management of infantile epileptic syndromes. Neurology 1993; 43(5 Suppl.) S21–3PubMedGoogle Scholar
  346. 346.
    Appleton RE, Hughes A, Beirne M, et al. Vigabatrin in the Landau-Kleffner Syndrome. Develop Med Child Neurol 1993; 35: 456–9Google Scholar
  347. 347.
    Gram L, Lyon BB, Down M. Gamma-vinyl-GABA: a single-blind trial in patients with epilepsy. Acta Neurol Scand 1983; 68: 34–9PubMedGoogle Scholar
  348. 348.
    Sivenius MRJ, Ylinen A, Murros K, et al. Double-blind dose reduction study of vigabatrin in complex partial epilepsy. Epilepsia 1987; 28: 688–92PubMedGoogle Scholar
  349. 349.
    McKee PJW, Blacklaw J, Friel E, et al. Adjuvant vigabatrin in refractory epilepsy: a ceiling to effective dosage in individual patients? Epilepsia 1993; 34: 937–43PubMedGoogle Scholar
  350. 350.
    Rundfeld C, Loscher W. Development of tolerance to the anticonvulsant effect of vigabatrin in amygdala-kindled rats. Eur J Pharmacol 1992; 213: 351–66Google Scholar
  351. 351.
    Pitkanen A, Ylinen A, Matilainen R, et al. Long-term antiepileptic efficacy of vigabatrin in drug-refractory epilepsy in mentally retarded patients. A 5-year follow-up study. Arch Neurol 1993; 50: 24–9PubMedGoogle Scholar
  352. 352.
    Ben-Menachem E, Persson LI, Mumford J. Long-term evaluation of once daily vigabatrin in drug-resistant partial epilepsy. Epilepsy Res 1990; 5: 240–6PubMedGoogle Scholar
  353. 353.
    Michelucci R, Rubboli G, Salvi F, et al. Long-term effect of vigabatrin in treatment of refractory epilepsy [abstract]. Epilepsia 1991; 32Suppl. 1: S11Google Scholar
  354. 354.
    Sander JWAS, Hart YM. Vigabatrin and behaviour disturbances [letter]. Lancet 1990; 335: 57PubMedGoogle Scholar
  355. 355.
    Sander JWAS, Hart Y, Trimble MR, et al. Vigabatrin and psychosis. J Neurol Neurosurg Psychiatry 1991; 54: 435–9PubMedGoogle Scholar
  356. 356.
    Ring HA, Trimble MR, Costa DC, et al. Effect of vigabatrin on striatal dopamine receptors: evidence in humans for interactions of GABA and dopamine systems. J Neurol Neurosurg Psychiatry 1992; 55: 758–61PubMedGoogle Scholar
  357. 357.
    Ring HA, Crellin R, Kirker S, et al. Vigabatrin and depression. J Neurol Neurosurg Psychiatry 1993; 56: 925–8PubMedGoogle Scholar
  358. 358.
    Dijkstra JB, McGuire AM, Trimble MR. The effect of vigabatrin on cognitive function and mood. Hum Psychopharmacol 1992; 7: 319–23Google Scholar
  359. 359.
    Gillham RA, Blacklaw J, McKee PJW, et al. Effect of vigabatrin on sedation and cognitive function in patients with refractory epilepsy. J Neurol Neurosurg Psychiatry 1993; 56: 1271–5PubMedGoogle Scholar
  360. 360.
    McGuire A, Duncan JS, Trimble MR. Effects of vigabatrin on cognitive function and mood when used as add-on therapy in patients with intractable epilepsy. Epilepsia 1992; 33: 128–34PubMedGoogle Scholar
  361. 361.
    Rogers D, Bird J, Eames P. Complex partial status after starting vigabatrin. Seizure 1993; 2: 155–6PubMedGoogle Scholar
  362. 362.
    Salke-Kellermann A, Baier H, Rambeck B, et al. Acute encephalopathy with vigabatrin [letter]. Lancet 1993; 342: 185PubMedGoogle Scholar
  363. 363.
    Jackson GD, Williams SR, van Bruggen N, et al. Vigabatrin-induced cerebellar and cortical lesions are demonstrated by quantitative MRI [abstract]. Epilepsia 1991; 32Suppl. 1: 13Google Scholar
  364. 364.
    Sussman NM, Weiss KL, Schroeder CE, et al. Vigabatrin: effects on in vivo and ex vivo magnetic resonance imaging of dog brains [abstract]. Epilepsia 1991; 32Suppl. 1: 13Google Scholar
  365. 365.
    Agosti R, Yarsargil G, Egli M, et al. Neuropathology of a human hippocampus following long-term treatment with vigabatrin: lack of micro vacuoles. Epilepsy Res 1990; 6: 166–70PubMedGoogle Scholar
  366. 366.
    Arezzo JC, Schroeder CE, Litwak MS, et al. Effects of vigabatrin on evoked potentials in dogs. Br J Clin Pharmacol 1989; 27: 53S–60SPubMedGoogle Scholar
  367. 367.
    Ben-Menachem E, Nordborg C, Hedstrom A, et al. Case report of surgical brain sample after 2 1/2 years of vigabatrin therapy [abstract]. Epilepsia 1988; 29: 699Google Scholar
  368. 368.
    Graham D. Neuropathology of vigabatrin. Br J Clin Pharmacol 1989; 27: 43S–5SPubMedGoogle Scholar
  369. 369.
    Paljarvi L, Vapalhti M, Sivenius J, et al. Neuropathological findings in 5 patients with vigabatrin treatment [abstract]. Neurology 1990; 40Suppl. 1: 153SGoogle Scholar
  370. 370.
    Jackson GD, Grunewald RA, Connelly A, et al. Quantitative MR relaxometry study of effects of vigabatrin on the brains of patients with epilepsy. Epilepsy Res. In pressGoogle Scholar
  371. 371.
    Hammond EJ, Wilder BJ. Effects of gamma-vinyl GABA on human pattern evoked visual potentials. Neurology 1985; 35: 1801–3PubMedGoogle Scholar
  372. 372.
    Brodie MJ, McKee PJW. Vigabatrin and psychosis [letter]. Lancet 1990; 335: 1279PubMedGoogle Scholar
  373. 373.
    Reynolds EH, Ring H, Heller A. A controlled trial of gamma-vinyl-GABA (vigabatrin) in drug resistant epilepsy [abstract]. Br J Clin Pract 1988; 42Suppl. 6: 33Google Scholar
  374. 374.
    Ring HA, Reynolds EH. Vigabatrin and behaviour disturbance [letter]. Lancet 1990; 335: 970PubMedGoogle Scholar
  375. 375.
    Ito T, Hori M, Masuda Y, et al. 2-Sulfamoylmethy1-1,2-benzisoxazole a new type of anticonvulsant drug. Arzneimittelforschung 1980; 30: 603–9PubMedGoogle Scholar
  376. 376.
    Masuda Y, Shiraishi Y, Karasawa T, et al. Differential antagonism of anticonvulsants to various components of maximal seizures induced by electroshock or pentylenetetrazole in mice. J Pharmaco Dynamics 1980; 3: 526–31Google Scholar
  377. 377.
    Seino M, Miyazaki H, Ito T. Zonisamide. In: Pisari F, Perruca E, Avanzini G, et al., editors. New antiepileptic drugs. Epilepsy Research Suppl. 3. Amsterdam: Elsevier Science Publishers, 1991: 169–74Google Scholar
  378. 378.
    Suzuki S, Kawakami K, Nishimura S, et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res 1992; 12: 21–7PubMedGoogle Scholar
  379. 379.
    Masuda Y, Karasawa T, Shiraishi Y, et al. 3-Sulfamoylmethyl-1,2-benzisoxazole, a new type of anticonvulsant drug. Arzneimittelforschung 1980; 30: 477–88PubMedGoogle Scholar
  380. 380.
    Uno H, Kurokawa M. Studies on 3-substituted 1,2-3- (sulfamoylmethyl)-1,2-benzisoxazole derivatives and their anticonvulsant activities. J Med Chem 1979; 22: 180–3PubMedGoogle Scholar
  381. 381.
    Hamoda K, Ishida S, Yagi K, et al. Anticonvulsant effects of zonisamide on amygdaloid kindling in rats. Neurosci 1990; 16: 407–12Google Scholar
  382. 382.
    Mimaki T, Tanoue H, Matsunaga Y, et al. Regional distribution of 14C-zonisamide in rat brain. Epilepsy Res 1994; 17: 233–6PubMedGoogle Scholar
  383. 383.
    Taylor CP, McLean JR, Bockbrader HN, et al. Zonisamide (AD-810, CI-912). In: Meldrum BS, Porter RJ, editors. New anticonvulsant drugs, current problems in epilepsy, Vol 4. London: John Libbey, 1986: 277–94Google Scholar
  384. 384.
    Wilensky AJ, Friel PN, Ojemann LM, et al. Pharmacokinetics of CI-912 in epileptic patients. In: Levy RH, Pitlick WH, Eichelbaum M, et al., editors. Metabolism of antiepileptic drugs. New York: Raven Press, 1984: 209–16Google Scholar
  385. 385.
    Ito T, Yamaguchi T, Miyazaki H, et al. Pharmacokinetic studies of AD-810, a new antiepileptic compound. Arzneimittelforschung 1982; 32: 1581–6PubMedGoogle Scholar
  386. 386.
    Masuda Y, Karasawa T. Inhibitory effect of zonisamide on human carbonic anhydrase in vitro. Arzneimittelforschung 1993; 43: 416–7PubMedGoogle Scholar
  387. 387.
    Matsumoto K, Miyazaki H, Fujii T, et al. Binding of sulfonamides to erythrocytes and their components. Chem Pharm Bull 1989; 37: 1913–5PubMedGoogle Scholar
  388. 388.
    Matsumoto K, Miyazaki H, Fujii T, et al. Absorption, distribution and excretion of 3-(sulphamoyl-[14C]methyl)-l,2-benzisoxazole (AD-810) in rats, dogs and monkeys and of AD-810 in man. Arzneimittelforschung 1983; 33: 961–8PubMedGoogle Scholar
  389. 389.
    Ojemann LM, Shastri RA, Wilensky AJ, et al. Comparative pharmacokinetics of zonisamide (CI-912) in epileptic patients on carbamazepine or phenytoin monotherapy. Ther Drug Monit 1986; 8: 293–6PubMedGoogle Scholar
  390. 390.
    Wagner JG, Sackellares JC, Donofrio PD, et al. Non-linear pharmacokinetics of CI-912 in adult epileptic patients. Ther Drug Monit 1984; 6: 277–82PubMedGoogle Scholar
  391. 391.
    Nishiguchi K, Ohnishi N, Iwakawa S, et al. Pharmacokinetics of zonisamide: a study in pediatric patients with refractory epilepsy. Jpn J Ther Drug Mon 1990; 7: 173–8Google Scholar
  392. 392.
    Nishiguchi K, Ohnishi N, Iwakawa S, et al. Pharmacokinetics of zonisamide; saturable distribution into human and rat erythrocytes and into rat brain. J Pharmacobiodyn 1992; 15: 409–15PubMedGoogle Scholar
  393. 393.
    Wilensky AJ, Friel PN, Ojemann LM, et al. Zonisamide in epilepsy: a pilot study. Epilepsia 1985; 26: 210–20Google Scholar
  394. 394.
    Ramsay RE, Wilder BJ, Sachellares J, et al. Multicentre study on the efficacy of zonisamide in the treatment of medically refractory complex partial seizures [abstract]. Epilepsia 1984; 25: 673Google Scholar
  395. 395.
    Sackellares JC, Donofrio PD, Wagner JG, et al. Pilot study of zonisamide (l,2-benzisoxazole-3-methanesulfonamide) in patients with refractory partial seizures. Epilepsia 1985; 26: 206–11PubMedGoogle Scholar
  396. 396.
    Yagi K, Seino M. Methodological requirements for clinical trials in refractory patients - our experience with zonisamide. Prog Neuropsychopharmacol Biol Psychiatry 1992; 16: 79–85PubMedGoogle Scholar
  397. 397.
    Iinuma K, Handa I, Fueki N, et al. Effects of zonisamide (AD-801) on refractory epilepsy in children; special reference to temporal lobe abnormalities. Curr Ther Res 1988; 43: 281–90Google Scholar
  398. 398.
    Oguni H, Hayakawa T, Fukayama Y. Clinical trial of zonisamide, a new antiepileptic drug, in cases of refractory childhood epilepsy. J Jpn Epilepsy Soc 1989; 7: 43–50Google Scholar
  399. 399.
    Sakamoto K, Kurokawa T, Tomita S, et al. Effects of zonisamide in children with epilepsy. Curr Ther Res 1988; 43: 378–83Google Scholar
  400. 400.
    Shuto H, Sugimoto T, Yasuhara A, et al. Efficacy of zonisamide in children with refractory partial seizures. Curr Ther Res Clin Exp 1989; 46: 1031–6Google Scholar
  401. 401.
    Takahashi I, Yamamoto N, Furune J, et al. Efficacy of zonisamide for intractable epilepsy in childhood. J Jpn Epilepsy Soc 1987; 5: 100–5Google Scholar
  402. 402.
    Henry TR, Leppik IE, Gumnit RJ, et al. Progressive myoclonus epilepsy treated with zonisamide. Neurology 1988; 38: 928–31PubMedGoogle Scholar
  403. 403.
    Leppik IE, Willmore LJ, Homan RW, et al. Efficacy and safety of zonisamide: results of a multicenter study. Epilepsy Res 1993; 14: 165–73PubMedGoogle Scholar
  404. 404.
    Schmidt D, Jabob R, Loiseau P, et al. Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial. Epilepsy Res 1993; 15: 67–73PubMedGoogle Scholar
  405. 405.
    Berent S, Sackellares C, Giordani B, et al. Zonisamide (CI-912) and cognition: results from preliminary study. Epilepsia 1987; 28: 61–7PubMedGoogle Scholar
  406. 406.
    Kimura S. Zonisamide-induced behavior disorder in two children. Epilepsia 1994; 35: 403–5PubMedGoogle Scholar
  407. 407.
    Bourgeois BFD. Antiepileptic potency and neurotoxicity of valproate alone and in combination with carbamazepine or phenobarbital. Clin Neuropharmacol 1988; 11: 348–59PubMedGoogle Scholar
  408. 408.
    Bourgeois BFD, Wad N. Combined administration of carbamazepine and phenobarbital: effect on anticonvulsant activity and neurotoxicity. Epilepsia 1988; 29: 482–7PubMedGoogle Scholar
  409. 409.
    Chez MG, Bourgeois BFD, Pippenger CE, et al. Pharmacodynamic interactions between phenytoin and valproate: individual and combined antiepileptic and neurotoxic action in mice. Clin Neuropharmacol 1994; 17: 32–7PubMedGoogle Scholar
  410. 410.
    Stringer JL, Higgins MG. Interaction of phenobarbital and phenytoin in an experimental model of seizures in rats. Epilepsia 1994; 35: 216–20PubMedGoogle Scholar
  411. 411.
    Rowan AJ, Meijer WA, de Beer-Pawlinkowski N, et al. Valproate-ethosuximide combination therapy for refractory absence seizure. Arch Neurol 1983; 40: 797–802PubMedGoogle Scholar
  412. 412.
    Gupta AK, Jeavons PM. Complex partial seizures: EEG foci and response to carbamazepine and sodium valproate. J Neurol Neurosurg Psychiatry 1985; 48: 1010–4PubMedGoogle Scholar
  413. 413.
    Ketter TA, Pazzaglia PJ, Post RM. Synergy of carbamazepine and valproic acid in affective illness: case report and review of the literature. J Clin Psychopharmacol 1992; 12: 276–81PubMedGoogle Scholar
  414. 414.
    Mireles R, Leppik IE. Valproate and clonazepam comedication in patients with intractable epilepsy. Epilepsia 1985; 26: 122–6PubMedGoogle Scholar
  415. 415.
    Panayiotopoulos GP, Ferrie CD, Knott C, et al. Interaction with lamotrigine and sodium valproate [letter]. Lancet 1993; 341: 445PubMedGoogle Scholar
  416. 416.
    Pisani F, Di Perri R, Perucca E, et al. Interaction of lamotrigine with sodium valproate [letter]. Lancet 1993; 341: 1224PubMedGoogle Scholar
  417. 417.
    Cereghino JJ, Brock JT, Van Meter JC, et al. The efficacy of carbamazepine combinations in epilepsy. Clin Pharmacol Ther 1975; 18: 733–41PubMedGoogle Scholar
  418. 418.
    Bittencourt PRM, Mazer S, Marcourakis T, et al. Vigabatrin: clinical evidence supporting rational polytherapy in management of uncontrolled seizures. Epilepsia 1994; 35: 373–80PubMedGoogle Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Philip N. Patsalos
    • 1
    • 2
  • John S. Duncan
    • 1
    • 2
  1. 1.Epilepsy Research GroupUniversity Department of Clinical Neurology, Institute of Neurology, National Hospital for Neurology and NeurosurgeryLondonEngland
  2. 2.National Society for Epilepsy, Chalfont Centre for EpilepsyChalfont St. PeterEngland

Personalised recommendations