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GABAA Receptor Agonists, Partial Agonists, and Antagonists

  • Chapter
The GABA Receptors

Part of the book series: The Receptors ((REC))

Abstract

The neutral amino acid, γ-aminobutyric acid (GABA), is an inhibitory transmitter in the central nervous system (CNS). Furthermore, GABA is involved as a neurotransmitter and/or a paracrine effector in the regulation of a variety of physiological mechanisms in the periphery. Some of these latter functions may be under central GABA control; others are managed by local GABA neurons. A large percentage, perhaps the majority, of central neurons are under GABA control. The complex mechanisms underlying the GABA-mediated neurotransmission have been extensively studied, using a broad spectrum of electrophysiological, neurochemical, pharmacological, and in recent years, molecular biological techniques (Krnjevic, 1974; Curtis and Johnston, 1974; Olsen and Venter, 1986; Redburn and Schousboe, 1987; Bowery and Nistico, 1989; Bowery et al., 1990; Biggio and Costa, 1990; Schousboe et al., 1992a).

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References

  • Allan, R. D., Apostopoulos, C., and Richardson, J. A. (1990) 2-Amino-1,3,4-thiadiazole derivatives of GABA as GABAA antagonists. Aust. J. Chem. 43, 1767–1772.

    Google Scholar 

  • Arnt, J. and Krogsgaard-Larsen, P. (1979) GABA agonists and potential antagonists related to muscimol. Brain Res 177, 395–400.

    PubMed  CAS  Google Scholar 

  • Barnard, E. A. (1992) Receptor classes and the transmitter-gated ion channels. Trends Biochem. Sci. 17, 368–374.

    PubMed  CAS  Google Scholar 

  • Barnard, E. A. and Costa, E., eds. (1989) Allosteric Modulation ofAmino Acid Receptors: Therapeutic Implications, Raven, New York.

    Google Scholar 

  • Baulieu, E. E. (1991) Neurosteroids: a new function in the brain. Biol. Cell. 71, 3–10.

    PubMed  CAS  Google Scholar 

  • Belhage, B., Damgaard, I., Saederup, E., Squires, R. F., and Schousboe, A. (1991) High-and low-affinity GABA-receptors in cultured cerebellar granule cells regulate transmitter release by different mechanisms. Neurochem. Int. 19, 475–482.

    CAS  Google Scholar 

  • Belhage, B., Hansen, G. H., Meier, E., and Schousboe, A. (1990) Effects of inhibitors of protein synthesis and intracellular transport on the GABAagonist induced functional differentiation of cultured cerebellar granule cells. J. Neurochem. 55, 1107–1113.

    PubMed  CAS  Google Scholar 

  • Benes, F. M., Vincent, S. L., Alsterberg, G., Bird, E. D., and SanGiovanni, J. P. (1992) Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics. J. Neurosci. 12, 924–929.

    Google Scholar 

  • Biggio, G. and Costa, E., eds. (1990) GAGA and Benzodiazepine Receptor Subtypes, Raven, New York.

    Google Scholar 

  • Bixler, E. O., Kales, A., Brubaker, B. H., and Kales, J. D. (1987) Adverse reactions to benzodiazepine hypnotics: spontaneous reporting system. Pharmacology 35, 286–300.

    PubMed  CAS  Google Scholar 

  • Bouchet, M.-J., Jacques, P., Ilien, B., Goeldner, M., and Hirth, C. (1992) m-Sulfonate benzene diazonium chloride: a powerful affinity label for the y-aminobutyric acid binding site from rat brain. J. Neurochem. 59, 1405–1413.

    Google Scholar 

  • Bowery, N. G. (1983) Classification of GABA receptors, in The GABA Receptors ( Enna, S. J., ed.), Humana, Clifton, NJ, pp. 177–213.

    Google Scholar 

  • Bowery, N. G., Bittiger, H., and Olpe, H.-R., eds. (1990) GABA B Receptors in Mammalian Function, John Wiley, Chichester.

    Google Scholar 

  • Bowery, N. G., Hill, D. R., Hudson, A. L., Doble, A., Middlemiss, D. N., Shaw, J., and Turnbull, M. (1980) (—) Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor. Nature 283, 92–94.

    Google Scholar 

  • Bowery, N. G. and Nistico, G., eds. (1989) GABA: Basic Research and Clinical Applications, Pythagora, Rome.

    Google Scholar 

  • Braestrup, C., Nielsen, M., Krogsgaard-Larsen, P., and Falch, E. (1979) Partial agonists for brain GABA/benzodiazepine receptor complex. Nature 280, 331–333.

    Google Scholar 

  • Brioni, J. D., Decker, M. W., Gamboa, L. P., Izquierdo, I., and McGaugh, J. L. (1990) Muscimol injections in the medial septum impair spatial learning. Brain Res. 522, 227–234.

    Google Scholar 

  • Brioni, J. D., Nagahara, A. H., and McGaugh, J. L. (1989) Involvement of the amygdala GABAergic system in the modulation of memory storage. Brain Res. 487, 105–112.

    PubMed  CAS  Google Scholar 

  • Brodie, M. J. and McKee, P. J. W. (1990) Vigabatrin and psychosis. Lancet 335, 1279.

    Google Scholar 

  • Bruno, G., Foster, N. L., Fedio, P., Mohr, E., Cox, C., Gillespie, M. M., and Chase, T. N. (1984) THIP therapy of Alzheimer’s disease. Neurology 34 (Suppl.) 225.

    Google Scholar 

  • Bureau, M. and Olsen, R. W. (1990) Multiple distinct subunits of the y-aminobutyric acid-A receptor protein show different ligand-binding affinities. Mol. Pharmacol. 37, 497–502.

    PubMed  CAS  Google Scholar 

  • Burke, D., Andrews, C. J., and Knowles, L. (1971) The action of a GABA derivative in human spasticity. J. Neurol. 14, 199–208.

    CAS  Google Scholar 

  • Byberg, J. R., Hjeds, H., Krogsgaard-Larsen, P., and Jorgensen, F. S. (1993) Conformational analysis and molecular modelling of a partial GABAA agonist and a glycine antagonist related to the GABAA agonist, THIP. Drug Des. Discovery 10, 213–229.

    CAS  Google Scholar 

  • Byberg, J. R., Labouta, I. M., Falch, E., Hjeds, H., Krogsgaard-Larsen, P., Curtis, D. R., and Gynther, B. D. (1987) Synthesis and biological activity of a GABA-A agonist which has no effect on benzodiazepine binding and structurally related glycine antagonists. Drug Des. Delivery 1, 261–274.

    CAS  Google Scholar 

  • Caspary, D. M., Raza, A., Lawhorn Armour, B. A., Pippin, J., and Arneric, S. P. (1990) Immunocytochemical and neurochemical evidence for age-related loss of GABA in the inferior colliculus: implications for neural presbycusis. J. Neurosci. 10, 2363–2372.

    PubMed  CAS  Google Scholar 

  • Cavalla, D. and Neff, N. H. (1985) Photoaffinity labeling of the GABAA receptor with [3H]muscimol. J. Neurochem. 44, 916–921.

    PubMed  CAS  Google Scholar 

  • Chambon, J.-P., Feltz, P., Heaulme, M., Restle, S., Schlichter, R., Biziere, K., and Wermuth, C. G. (1985) An arylaminopyridazine derivative of y-aminobutyric acid (GABA) is a selective and competitive antagonist of the receptor sites. Proc. Natl. Acad. Sci. USA 82, 1832–1836.

    PubMed  CAS  Google Scholar 

  • Cherubini, E., Gaiarsa, J. L., and Ben-Ari, Y. (1991) GABA: an excitatory transmitter in early postnatal life. Trends Neurosci. 14, 515–519.

    PubMed  CAS  Google Scholar 

  • Curtis, D. R., Duggan, A. W., Felix, D., and Johnston, G. A. R. (1970) GABA, bicuculline and central inhibition. Nature 226, 1222–1224.

    PubMed  CAS  Google Scholar 

  • Curtis, D. R., Game, C. J. A., Johnston, G. A. R., and McCulloch, R. M. (1974) Central effects of ß-(p-chlorophenyl)-y-aminobutyric acid. Brain Res. 70, 493–499.

    PubMed  CAS  Google Scholar 

  • Curtis, D. R. and Johnston, G. A. R. (1974) Amino acid transmitters in the mammalian central nervous system. Ergebn. Physiol. 69, 97–188.

    PubMed  CAS  Google Scholar 

  • Cutting, G. R., Lu, L., O’Hara, B. F., Kasch, L. M., Montrose-Rafizaheh, C., Donovan, D. M., Shimada, S., Antonorakis, S. E., Guggino, W. B., Uhl, G. R., and Kazazian, H. H. (1991) Cloning of the y-aminobutyric acid (GABA) r1 cDNA: a GABA receptor subunit highly expressed in retina. Proc. Natl. Acad. Sci. USA 88, 2673–2677.

    PubMed  CAS  Google Scholar 

  • Dannhardt, G., Dominiak, P., and Laufer, S. (1993) Hypertensive effects and structure-activity relationships of 5-w-aminoalkyl isoxazoles. Drug Res. 43, 441–444.

    CAS  Google Scholar 

  • DeErasquin, G., Grooker, G., Costa, E., and Woscik, W. J. (1992) Stimulation of high affinity y-aminobutyric acide receptors potentiates the depolarization induced increase

    Google Scholar 

  • of intraneuronal ionised calcium content in cerebellar granule neurons. Mol. Pharmacol. 42 407–414.

    Google Scholar 

  • DeFeudis, F. V. (1989) GABA agonists and analgesia. Drug News Perspect. 2, 172, 173.

    Google Scholar 

  • DeLorey, T. M. and Olsen, R. W. (1992) y-Aminobutyric acid, receptor structure and function. J. Biol. Chem. 267, 16,747–16, 750.

    Google Scholar 

  • DiChiara, G. and Gessa, G. L., eds. (1981) GAGA and the Basal Ganglia, Raven, New York.

    Google Scholar 

  • Djamgoz, M. B. A. (1995) Diversity of GABA receptors in the vertebrate outer retina. Trends Neurosci. 18, 118–120.

    CAS  Google Scholar 

  • Drew, C. A. and Johnston, G. A. R. (1992) Bicuculline-and baclofen-insensitive y-amino- butyric acid binding to rat cerebellar membranes. J. Neurochem. 58, 1087–1092.

    PubMed  CAS  Google Scholar 

  • Ebert, B., Brehm, L., Wafford, K. A., Kristiansen, U., Kemp, J. A., and KrogsgaardLarsen, P. (1996) Structure and molecular pharmacology of thio-THIP. Eur. J. Med. Chem., submitted.

    Google Scholar 

  • Ebert, B., Wafford, K. A., Whiting, P. J., Krogsgaard-Larsen, R, and Kemp, J. A. (1994) Molecular pharmacology of y-aminobutyric acid type A receptor agonists and partial agonists in oocytes injected with different a, ß and y receptor subunit combinations. Mol. Pharmacol. 46, 957–963.

    PubMed  CAS  Google Scholar 

  • Edvinsson, L., Larsson, B., and Skarby, T. (1980) Effect of the GABA receptor agonist muscimol on regional cerebral blood flow in the rat. Brain Res. 185, 445–448.

    PubMed  CAS  Google Scholar 

  • Erdo, S. L. (1985) Peripheral GABAergic mechanisms. Trends Pharmacol. Sci. 6, 205–208.

    Google Scholar 

  • Erdo, S. L. and Bowery, N. G., eds. (1986) GABAergic Mechanisms in Mammalian Periphery, Raven, New York.

    Google Scholar 

  • Falch, E., Hedegaard, A., Nielsen, L., Jensen, B. R., Hjeds, H., and Krogsgaard-Larsen, P. (1986) Comparative stereostructure-activity studies on GABA, and GABAB receptor sites and GABA uptake using rat brain membrane preparations. J. Neurochem. 47, 898–903.

    Google Scholar 

  • Falch, E., Larsson, O. M., Schousboe, A., and Krogsgaard-Larsen, P. (1990) GABA-A agonists and GABA uptake inhibitors: structure-activity relationships. Drug Dey. Res. 21, 169–188.

    CAS  Google Scholar 

  • Fariello, R. G., Morselli, P. L., Lloyd, K. G., Quesney, L. F., and Engel, J., eds. (1984) Neurotransmitters, Seizures, and Epilepsy II, Raven, New York.

    Google Scholar 

  • Feigenspan, A., Wassle, H., and Bormann, J. (1993) Pharmacology of GABA receptor Cl-channels in rat retinal bipolar cells. Nature 361, 159–162.

    PubMed  CAS  Google Scholar 

  • Foster, N. L., Chase, T. N., Denaro, A., Hare, T. A., and Tamminga, C. A. (1983) THIP treatment and Huntington’s chorea. Neurology 33, 637–639.

    PubMed  CAS  Google Scholar 

  • Friedman, D. E. and Redburn, D. A. (1990) Evidence for functionally distinct subclasses of y-aminobutyric acid receptors in rabbit retina. J. Neurochem. 55, 1189–1199.

    PubMed  CAS  Google Scholar 

  • Froestl, W., Mickel, S. J., Hall, R. G., von Sprecher, G., Strub, D., Baumann, P. A., Bragger, F., Gentsch, C., Jaekel, J., Olpe, H.-R., Rihs, G., Vassout, A., Waldmeier, P. C., and Bittiger, H. (1995a) Phosphinic acid analogues, of GABA. 1. New potent and selective GABAB agonists. J. Med. Chem. 38, 3297–3312.

    PubMed  CAS  Google Scholar 

  • Froestl, W., Mickel, S. J., von Sprecher, G., Diel, P. J., Hall, R. G., Maier, L., Strub, D., Melillo, V., Baumann, R A., Bemasconi, R., Gentsch, C., Hauser, K., Jaekel, J., Karlsson, G., Klebs, K., Maître, L., Marescaux, C., Pozza, M. F., Schmutz, M., Steinmann, M. W., van Riezen, H., Vassout, A., Mondadori, C., Olpe, H.-R., Waldmeier, R C., and Bittiger, H. (1995b) Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists. J. Med. Chem. 38, 3313–3331.

    PubMed  CAS  Google Scholar 

  • Frolund, B., Ebert, B., Lawrence, L. W., Hurt, S. D., and Krogsgaard-Larsen, P. (1995a) Synthesis and receptor binding of 5-amino[3H]2methyl-3-isothiazolol ([3H]thiomuscimol), a specific GABAA agonist photoaffinity label. J. Labelled Compd. Radiopharm. 36, 877–889.

    CAS  Google Scholar 

  • Frolund, B., Jeppesen, L., Krogsgaard-Larsen, P., and Hansen, J. J. (1995b) GABAA agonists: resolution and pharmacology of (+)- and (—)-isoguvacine oxide. Chirality 7, 434–438.

    Google Scholar 

  • Frolund, B., Kristiansen, U., Brehm, L., Hansen, A. B., Krogsgaard-Larsen, P., and Falch, E. (1995c) Partial GABAA receptor agonists. Synthesis and in vitro pharmacology of a series of nonannulated analogs of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol. J. Med. Chem. 38, 3287–3296.

    PubMed  CAS  Google Scholar 

  • Frolund, B. F., Kristiansen, U., Nathan, T., Falch, E., Lambert, J. D. C., and KrogsgaardLarsen, R (1992) 4-PIOL, a low-efficacy partial GABAA agonist, in Drug Research Related to Neuroactive Amino Acids, Alfred Benzon Symposium 32 (Schousboe, A., Diemer, N. H., and Kofod, H., eds.), Munksgaard, Copenhagen, pp. 449–460.

    Google Scholar 

  • Frydenvang, K., Krogsgaard-Larsen, R, Hansen, J. J., Mitrovic, A., Tran, H., Drew, C. A., and Johnston, G. A. R. (1994) GABAB antagonists: resolution, absolute stereochemistry and pharmacology of (R)- and (S)-phaclofen. Chirality 6, 583–589.

    PubMed  CAS  Google Scholar 

  • Gammill, R. B. and Carter, D. B. (1993) Neuronal BZD receptors: new ligands, clones and pharmacology. Annu. Rep. Med. Chem. 28, 19–27.

    CAS  Google Scholar 

  • Guidotti, A. (1992) Imidazenil: a new partial positive allosteric modulator of the GABAA receptor. Neurosci. Facts 3, 71–72.

    Google Scholar 

  • Günther, U., Benson, J., Benke, D., Fritschy, J.-M., Reyes, G., Knoflach, F., Crestani, F., Aguzzi, A., Arigoni, M., Lang, Y., Bluethmann, H., Möhler, H., and Luscher, B. (1995) Benzodiazepine-insensitive mice generated by targeted disruption of the y2 subunit gene of y-aminobutyric acid type A receptors. Proc. Natl. Acad. Sci. USA 92, 7749–7753.

    Google Scholar 

  • Haefely, W. (1984) Pharmacological profile of two benzodiazepine partial agonists: Ro 16–6028 and Ro 17–1812. Clin. Neuropharmacol. 7 (Suppl. 1) 670–671.

    Google Scholar 

  • Haefely, W. and Polc, P. (1986) Physiology of GABA enhancement by benzodiazepines and barbiturates, in Benzodiazepine/GABA Receptors and Chloride Channels: Structural and Functional Properties (Olsen, R. W., Venter, J. C., eds.), Alan R. Liss, New York, pp. 97–133.

    Google Scholar 

  • Hahner, L., McQuilkin, S., and Harris, R. A. (1991) Cerebellar GABAB receptors modulate function of GABAA receptors. FASEB J. 5, 2466–2472.

    PubMed  CAS  Google Scholar 

  • Hall, R. C. and Zisool, S. (1981) Paradoxical reactions to benzodiazepines. Br. J. Clin. Pharmacol. 11, 99S - 1045.

    PubMed  Google Scholar 

  • Hanada, S., Mita, S., Nishino, N., and Tanaka, C. (1987) [3H]Muscimol binding sites increased in autopsied brains of chronic schizophrenics. Life Sci. 40, 259–266.

    Google Scholar 

  • Hansen, G. H., Belhage, B., and Schousboe, A. (1992) First direct electron microscopic visualization of a tight spatial coupling between GABAA-receptors and voltage sensitive calcium channels. Neurosci. Lett. 137, 14–18.

    PubMed  CAS  Google Scholar 

  • Harrison, N. L. and Simmonds, M. A. (1984) Modulation of the GABA receptor complex by a steroid anaesthetic. Brain Res. 323, 287–292.

    PubMed  CAS  Google Scholar 

  • Hoehn-Saric, R. (1983) Effects of THIP on chronic anxiety. Psychopharmacology 80, 338–341.

    PubMed  CAS  Google Scholar 

  • Hunkeler, W., Möhler, H., Pieri, L., Polc, R, Bonetti, E. R, Cumin, R., Schaffner, R., and Haefely, W. (1981) Selective antagonists of benzodiazepines. Nature 290, 514–516.

    PubMed  CAS  Google Scholar 

  • Huston, E., Gullen, G., Sweeney, M. I., Pearson, H., Fazeli, M. S., and Dolphin, A. C. (1993) Pertussis toxin treatment increases glutamate release and dihydropyridine binding sites in cultured rat cerebellar granule neurons. Neuroscience 52, 787–798.

    PubMed  CAS  Google Scholar 

  • Huston, E., Scott, R. H., and Dolphin, A. C. (1990) A comparison of the effect of calcium channel ligands and GABAB agonists and antagonists in transmitter release and somatic calcium currents in cultured neurons. Neuroscience 38, 721–729.

    PubMed  CAS  Google Scholar 

  • Johnston, G. A. R. (1986) Multiplicity of GABA receptors, in Benzodiazepine/GABA Receptors and Chloride Channels: Structural and Functional Properties ( Olsen, R. W. and Venter, J. C., eds.), Alan R. Liss, New York, pp. 57–71.

    Google Scholar 

  • Johnston, G. A. R., Beart, P. M., Curtis, D. R., Game, C. J. A., McCulloch, R. M., and MacLachlan, R. M. (1972) Bicuculline methochloride as a GABA antagonist. Nature (New Biol.) 240, 219, 220.

    Google Scholar 

  • Johnston, G. A. R., Curtis, D. R., Beart, P. M., Game, C. J. A., McCulloch, R. M., and Twitchin, B. (1975a) Cis-and Trans-4-aminocrotonic acid as GABA analogues of restricted conformation. J. Neurochem. 24, 157–160.

    PubMed  CAS  Google Scholar 

  • Johnston, G. A. R., Krogsgaard-Larsen, P., and Stephanson, A. (1975b) Betel nut constituents as inhibitors of y-aminobutyric acid uptake. Nature 258, 627–628.

    PubMed  CAS  Google Scholar 

  • Kardos, J., Elster, L., Damgaard, I., Krogsgaard-Larsen, P., and Schousboe, A. (1994) Role of GABAB receptors in intracellular Cat+ homeostasis and possible interaction between GABAA and GABAB receptors in regulation of transmitter release in cerebellar granule neurons. J. Neurosci. Res. 39, 646–655.

    Google Scholar 

  • Kendall, D. A., Browner, M., and Enna, S. J. (1982) Comparison of the antinociceptive effect of GABA agonists: evidence for a cholinergic involvement. J. Pharmacol. Exp. Ther. 220, 482–487.

    PubMed  CAS  Google Scholar 

  • Kerr, D. I. B. and Ong, J. (1986) GABAB-receptors in peripheral function, in GABAergic Mechanisms in Mammalian Periphery ( Erdo, S. L. and Bowery, N. G., eds.), Raven, New York, pp. 239–259.

    Google Scholar 

  • Kerr, D. I. B., Ong, J., Prager, R. H., Gynther, B. D., and Curtis, D. R. (1987) Phaclofen: a peripheral and central baclofen antagonist. Brain Res. 405, 150–154.

    PubMed  CAS  Google Scholar 

  • Kiuchi, Y., Kobayashi, T., Takeuchi, J., Shimuzu, H., Ogata, H., and Toni, M. (1989) Benzodiazepine receptors increase in post-mortem brain of chronic schizophrenics. Eur. Arch. Psychiat. Neurol. Sci. 239, 71–78.

    Google Scholar 

  • Korpi, E. R., Uusi-Oukari, M., and Wegelius, K. (1992) Substrate specificity of diazepam-insensitive cerebellar [3H]Ro 15–4513 binding sites. Eur. J. Pharmacol. 213, 323–329.

    PubMed  CAS  Google Scholar 

  • Korsgaard, S., Casey, D. E., Gerlach, J., Hetmar, O., Kaldan, B., and Mikkelsen, L. B. (1982) The effect of tetrahydroisoxazolopyridinol (THIP) in tardive dyskinesia. Arch. Gen. Psychiatry 39, 1017–1021.

    PubMed  CAS  Google Scholar 

  • Kristiansen, U., Hedegaard, A., Herdeis, C., Lund, T. M., Nielsen, B., Hansen, J. J., Falch, E., Hjeds, H., and Krogsgaard-Larsen, P. (1992) Hydroxylated analogues of 5-aminovaleric acid as 4-aminobutyric acidB receptor antagonists: stereostructureactivity relationships. J. Neurochem. 58, 1150–1159.

    PubMed  CAS  Google Scholar 

  • Kristiansen, U., Lambert, J. D. C., Falch, E., and Krogsgaard-Larsen, P. (1991) Electrophysiological studies of the GABAA receptor ligand, 4-PIOL, on cultured hippocampal neurones. Br. J. Pharmacol. 104, 85–90.

    Google Scholar 

  • Krnjevic, K. (1974) Chemical nature of synaptic transmission in vertebrates. Physiol. Rev. 54, 418–540.

    CAS  Google Scholar 

  • Krogsgaard-Larsen, P. (1988) GABA synaptic mechanisms: stereochemical and conformational requirements. Med. Res. Rev. 8, 27–56.

    PubMed  CAS  Google Scholar 

  • Krogsgaard-Larsen, P., Falch, E., and Christensen, A. V. (1984) Chemistry and pharmacology of the GABA agonists THIP (Gaboxadol) and isoguvacine. Drugs Fut. 9, 597–618.

    Google Scholar 

  • Krogsgaard-Larsen, P., Falch, E., and Hjeds, H. (1985) Heterocyclic analogues of GABA: chemistry, molecular pharmacology and therapeutic aspects. Prog. Med. Chem. 22, 67–120.

    PubMed  CAS  Google Scholar 

  • Krogsgaard-Larsen, P., Falch, E., Larsson, O. M., and Schousboe, A. (1987) GABA up- take inhibitors: relevance to antiepileptic drug research. Epilepsy Res. 1, 77–93.

    PubMed  CAS  Google Scholar 

  • Krogsgaard-Larsen, P., Frolund, B., Jorgensen, F. S., and Schousboe, A. (1994) GABAA receptor agonists, partial agonists, and antagonists. Design and therapeutic prospects. J. Med. Chem. 37, 2489–2505.

    PubMed  CAS  Google Scholar 

  • Krogsgaard-Larsen, P. and Hansen, J. J., eds. (1992) Excitatory Amino Acid Receptors: Design ofAgonists and Antagonists, Ellis Horwood, Chichester, UK.

    Google Scholar 

  • Krogsgaard-Larsen, P., Hjeds, H., Curtis, D. R., Lodge, D., and Johnston, G. A. R. (1979) Dihydromuscimol, thiomuscimol and related heterocyclic compounds as GABA analogues. J. Neurochem. 32, 1717–1724.

    PubMed  CAS  Google Scholar 

  • Krogsgaard-Larsen, P., Hjeds, H., Falch, E., Jorgensen, F. S., and Nielsen, L. (1988) Recent advances in GABA agonists, antagonists and uptake inhibitors: structure-activity relationships and therapeutic potential. Adv. Drug Res. 17, 381–456.

    CAS  Google Scholar 

  • Krogsgaard-Larsen, P., Jacobsen, P., Brehm, L., Larsen, J.-J., and Schaumburg, K. (1980) GABA agonists and uptake inhibitors designed as agents with irreversible actions. Eur. J. Med. Chem. 15, 529–535.

    CAS  Google Scholar 

  • Krogsgaard-Larsen, P. and Johnston, G. A. R. (1975) Inhibition of GABA uptake in rat brain slices by nipecotic acid, various isoxazoles and related compounds. J Neurochem. 25, 797–802.

    PubMed  CAS  Google Scholar 

  • Krogsgaard-Larsen, P., Johnston, G. A. R., Lodge, D., and Curtis, D. R. (1977) A new class of GABA agonist. Nature 268, 53–55.

    PubMed  CAS  Google Scholar 

  • Krogsgaard-Larsen, P., Mikkelsen, H., Jacobsen, P., Falch, E., Curtis, D. R., Peet, M. J., and Leah, J. D. (1983) 4,5,6,7-Tetrahydroisothiazolo[5,4-c]pyridin-3-ol and related analogues of THIP. Synthesis and biological activity. J. Med. Chem. 26, 895–900.

    Google Scholar 

  • Krogsgaard-Larsen, P., Nielsen, L., Falch, E., and Curtis, D. R. (1986) GABA agonists. Resolution, absolute stereochemistry, and enantioselectivity of (S)-(+)- and (R)-(—) dihydromuscimol. J. Med. Chem. 28, 1612–1617.

    Google Scholar 

  • Krogsgaard-Larsen, P., Snowman, A., Lummis, S. C., and Olsen, R. W. (1981) Characterization of the binding of the GABA agonist [3H]piperidine-4-sulfonic acid to bovine brain synaptic membranes. J. Neurochem. 37, 401–409.

    PubMed  CAS  Google Scholar 

  • Lambert, J. J., Belelli, D., Hill-Venning, C., and Peters, J. A. (1995) Neurosteroids and GABAA receptor function. Trends Pharmacol. Sci. 16, 295–303.

    PubMed  CAS  Google Scholar 

  • Levi, G. and Gallo, V. (1981) Glutamate as a putative transmitter in the cerebellum: stimulation by GABA of glutamic acid release from specific pools. J. Neurochem. 37, 22–31.

    PubMed  CAS  Google Scholar 

  • Lodge, D., ed. (1988) Excitatory Amino Acids in Health and Disease, John Wiley, Chichester, UK.

    Google Scholar 

  • Lopez, I., Wu, J. Y., and Meza, G. (1992) Immunocytochemical evidence for an afferent GABAergic neurotransmission in the guinea pig vestibular system. Brain Res. 589, 341–348.

    PubMed  CAS  Google Scholar 

  • Loscher, W. (1989) GABA and the epilepsies. Experimental and clinical conditions, in GABA: Basic Research and Clinical Applications ( Bowery, N. G. and Nistico, G., eds.), Pythagora, Rome, pp. 260–300.

    Google Scholar 

  • Lüddens, H., Pritchett, D. B., Kohler, M., Killisch, I., Keinänen, K., Moneyer, H., Sprengel, R., and Seeburg, P. H. (1990) Cerebellar GABAA receptor selective for a behavioural alcohol antagonist. Nature 346, 648–651.

    PubMed  Google Scholar 

  • Macdonald, R. L. and Olsen, R. W. (1994) GABAA receptor channels. Annu. Rev. Neurosci. 17, 569–602.

    PubMed  CAS  Google Scholar 

  • Maksay, G. (1994) Thermodynamics of y-aminobutyric acid type A receptor binding differentiate agonists from antagonists. Mol. Pharmacol. 46, 386–390.

    PubMed  CAS  Google Scholar 

  • Malcangio, M., Malmberg-Aiello, P., Giotti, A., Ghelardini, C., and Bartolini, A. (1992) Desensitization of GABA, receptors and antagonism by CGP 35348 prevent bicucullineand picrotoxin-induced antinociception. Neuropharmacology 31, 783–791.

    PubMed  CAS  Google Scholar 

  • Malminiemi, O. and Korpi, E. S. (1989) Diazepam-insensitive [3H]Ro 15–4513 binding in intact cultured cerebellar granule cells. Eur. J. Pharmacol. 169, 53–60.

    PubMed  CAS  Google Scholar 

  • Mathers, D. A. (1987) The GABAA receptor: new insights from single-channel recording. Synapse 1, 96–101.

    PubMed  CAS  Google Scholar 

  • McNeil, R. G., Gee, K. W., Bolger, M. B., Lan, N. C., Wieland, S., Belelli, D., Purdy, R. H., and Paul, S. M. (1992) Neuroactive steroids that act at GABAA receptors. Drug News Perspect. 5, 145–152.

    Google Scholar 

  • Meier, E., Drejer, J., and Schousboe, A. (1984) GABA induces functionally active low-affinity GABA receptors on cultured cerebellar granule cells. J. Neurochem. 43, 17371744.

    Google Scholar 

  • Meldrum, B. (1982) GABA and acute psychoses. Psychol. Med. 12, 1–5.

    PubMed  CAS  Google Scholar 

  • Melikian, A., Schlewer, G, Chambon, J.-P., and Wermuth, C. G. (1992) Condensation of muscimol or thiomuscimol with aminopyridazines yields GABA-A antagonists. J. Med. Chem. 35, 4092–4097.

    PubMed  CAS  Google Scholar 

  • Merz, W. A., Alterwain, P., Ballmer, U., Bechelli, L., Capponi, R., Munoz, J. G., Marquez, C., Nestoros, J., Almanzor, L. R., Udabe, R. U., and Versiani, M. (1988) Treatment of paranoid schizophrenia with the partial benzodiazepine agonist, Ro 16–6028. Psychopharmacol. 95–96 (Suppl.), 237.

    Google Scholar 

  • Minchin, M. C. W., Ennis, C., Lattimer, N., White, J. F., White, A. C., and Lloyd, K. G. (1992a) The GABAA-like autoreceptor is a pharmacologically novel GABA receptor, in GABAergic Synaptic Transmission ( Biggio, G., Concas, A., and Costa, E., eds.), Raven, New York, pp. 199–203.

    Google Scholar 

  • Minchin, M. C. W., White, A. C., and White, J. F. (1992b) Novel GABA autoreceptor antagonists. Current Drugs 2, 1878–1880.

    Google Scholar 

  • Mitchell, R. (1980) A novel GABA receptor modulates stimulus induced glutamate release from cortico-striatal terminals. Eur. J. Pharmacol. 67, 119–122.

    PubMed  CAS  Google Scholar 

  • Möhler, H., Knoflach, F., Paysan, J., Motejlek., K., Benke, D., Luscher, B., and Fritschy, J. M. (1995) Heterogeneity of GABAA-receptors: cell-specific expression, pharmacology, and regulation. Neurochem. Res. 20, 631–636.

    Google Scholar 

  • Möhler, H. and Okada, T. (1977) Benzodiazepine receptors: demonstration in the central nervous system. Science 198, 849–851.

    PubMed  Google Scholar 

  • Morselli, P. L., Loscher, W., Lloyd, K. G., Meldrum, B., and Reynolds, E. H., eds. (1981) Neurotransmitters, Seizures, and Epilepsy, Raven, New York.

    Google Scholar 

  • Nayeem, N., Green, T. P., Martin, I. L., and Barnard, E. A. (1994) Quaternary structure of the native GABAA receptor determined by electron microscopic image analysis. J. Neurochem. 62, 815–818.

    PubMed  CAS  Google Scholar 

  • Nielsen, E. O., Aarslew-Jensen, M., Diemer, N. H., Krogsgaard-Larsen, P., and Schousboe, A. (1989) Baclofen-induced, calcium-dependent stimulation of in vivo release of D-[3HJaspartate from rat hippocampus monitored by intracerebral microdialysis. Neurochem. Res. 14, 321–326.

    PubMed  CAS  Google Scholar 

  • Nielsen, L., Brehm, L., and Krogsgaard-Larsen, P. (1990) GABA agonists and uptake inhibitors. Synthesis, absolute stereochemistry, and enantioselectivity of (R)-(—)- and (S)-(+)-homo-ß-proline. J. Med. Chem. 33 71–77.

    Google Scholar 

  • Nielsen, M., Witt, M.-R., Ebert, B., and Krogsgaard-Larsen, P. (1995) Thiomuscimol, a new photoaffinity label for the GABAA receptor. Eur. J. Pharmacol. Mol. Pharmacol. Sect. 289, 109–112.

    Google Scholar 

  • Nistico, G., Morselli, P. L., Lloyd, K. G., Fariello, R. G., and Engel, J., eds. (1986) Neurotransmitters, Siezures, and Epilepsy III, Raven, New York.

    Google Scholar 

  • Olsen, R. W., Bureau, M. H., Edno, S., and Smith, G. (1991) The GABAA receptor family in the mammalian brain. Neurochem. Res. 16, 317–325.

    PubMed  CAS  Google Scholar 

  • Olsen, R. W. and Tobin, A. J. (1990) Molecular biology of GABAA receptors. FASEB J. 4, 1469–1480.

    Google Scholar 

  • Olsen, R. W. and Venter, J. C., eds. (1986) Benzodiazepine/GABA Receptors and Chloride Channels: Structural and Functional Properties, Alan R. Liss, New York.

    Google Scholar 

  • Ong, J. and Kerr, D. I. B. (1990) GABA-receptors in peripheral tissues. Life Sci. 46, 1489–1501.

    PubMed  CAS  Google Scholar 

  • Ong, J., Kerr, D. I. B., Capper, H. R., and Johnston, G. A. R. (1990) Cortisone, a potent GABAA antagonist in the guinea-pig isolated ileum. J. Pharm. Pharmacol. 42, 662–664.

    PubMed  CAS  Google Scholar 

  • Ong, J., Kerr, D. I. B., and Johnston, G. A. R. (1987) Cortisol: a potent biphasic modulator at GABAA-receptor-complexes in the guinea-pig isolated ileum. Neurosci. Lett. 82, 101–106.

    PubMed  CAS  Google Scholar 

  • Palay, S. and Chan-Palay, V. (1982) The cerebellum-new vistas. Exp. Brain. Res. Suppl. 6, 1–620.

    Google Scholar 

  • Petersen, H. R., Jensen, I., and Dam, M. (1983) THIP: a single-blind controlled trial in patients with epilepsy. Acta Neurol. Scand. 67, 114–117.

    CAS  Google Scholar 

  • Peyron, R., Cinotti, L., Le Bars, D., Garcia-Larrea, L., Galy, G., Landais, P., Millet, P., Lavenne, F., Froment, J. C., Krogsgaard-Larsen, F., and Mauguiere, F. (1994b) Effects of GABAA receptor activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study. II. The focal hypometabolism is reactive to GABAA agonist administration in TLE. Epilepsy Res. 19, 55–62.

    Google Scholar 

  • Peyron, R., Le Bars, D., Cinotti, L., Garcia-Larrea, L., Galy, G., Landais, P., Millet, P., Lavenne, F., Froment, J. C., Krogsgaard-Larsen, P., and Mauguiere, F. (1994a) Effects of GABAA receptor activation on brain glucose metabolism in normal subjects and temporal lope epilepsy (TLE) patients. A positron emission tomography (PET) study. I. Brain glucose metabolism is increased after GABAA receptors activation. Epilepsy Res. 19, 45–54.

    PubMed  CAS  Google Scholar 

  • Prince, R. J. and Simmonds, M. A. (1993) Differential antagonism by epipregnanolone of alphaxalone and pregnanolone potentiation of [3H]flunitrazepam binding suggests more than one class of binding site for steroids at GABAA receptors. Neuropharmacology 32, 59–63.

    PubMed  CAS  Google Scholar 

  • Qian, H. and Dowling, J. E. (1993a) Novel GABA responses from rod-driven retinal horizontal cells. Nature 361, 162–164.

    PubMed  CAS  Google Scholar 

  • Qian, H., and Dowling, J. E. (1993b) GABA responses on retinal bipolar cells. Biol. Bull. 185 312.

    Google Scholar 

  • Qian, H. and Dowling, J. E. (1994) Pharmacology of novel GABA receptors found on rod horizontal cells of the white perch retina. J. Neurosci. 14, 4299–4307.

    PubMed  CAS  Google Scholar 

  • Redburn, D. A. and Schousboe, A., eds. (1987) Neurotrophic Activity of GABA During Development, Alan R. Liss, New York.

    Google Scholar 

  • Ring, H. A. and Reynolds, E. H. (1990) Vigabatrin and behaviour disturbance. Lancet 335, 970.

    PubMed  CAS  Google Scholar 

  • Roberts, E. (1976) Disinhibition as an organizing principle in the nervous system—the role of the GABA system. Application to neurologic and psychiatric disorders, in GABA in Nervous System Function ( Roberts, E., Chase, T. N., and Tower, D. B., eds.), Raven, New York, pp. 515–539.

    Google Scholar 

  • Roberts, E. (1986) GABA: the road to neurotransmitter status, in Benzodiazepine/GABA Receptors and Chloride Channels: Structural and Functional Properties ( Olsen, R. W., and Venter, J. C., eds.), Alan R. Liss, New York, pp. 1–39.

    Google Scholar 

  • Roberts, E. (1991) Living systems are tonically inhibited, autonomous optimizers, and disinhibition coupled to a variability generation is their major organizing principle: inhibitory command-control at levels of membrane, genome, metabolism, brain, and society. Neurochem. Res. 16, 409–421.

    PubMed  CAS  Google Scholar 

  • Robinson, M. K., Richens, A., and Oxley, R. (1990) Vigabatrin and behaviour disturbances. Lancet 336, 504.

    PubMed  CAS  Google Scholar 

  • Rognan, D., Boulanger, T., Hoffmann, R., Vercauteren, D. P., Andre, J.-M., Durant, F., and Wermuth, C. G. (1992) Structure and molecular modeling of GABAA receptor antagonists. J. Med. Chem. 35, 1969–1977.

    Google Scholar 

  • Roland, P. E. and Friberg, L. (1988) The effect of the GABAA agonist THIP on regional cortical blood flow in humans. A new test of hemispheric dominans. J. Cereb. Blood Flow Metab. 8, 314–323.

    PubMed  CAS  Google Scholar 

  • Rorsman, P., Berggren, P.-O., Bokvist, K., Ericson, H., Möhler, H., Ostenson, C.-G., and Smith, P. A. (1989) Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels. Nature 341, 233–236.

    PubMed  CAS  Google Scholar 

  • Ryan, A. F. and Schwartz, I. R. (1986) Nipecotic acid: preferential accumulation in the cochlea by GABA uptake systems and selective retrograde transport to brainstem. Brain Res. 399, 399–403.

    PubMed  CAS  Google Scholar 

  • Saito, A., Wu, J. Y., and Lee, T. J. (1985) Evidence for the presence of cholinergic nerves in cerebral arteries: an immunohistochemical demonstration of choline acetyltransferase. J. Cereb. Blood Flow Metab. 5, 327–334.

    PubMed  CAS  Google Scholar 

  • Sander, J. W. and Hart, Y. M. (1990) Vigabatrin and behaviour disturbances. Lancet 335, 57.

    PubMed  CAS  Google Scholar 

  • Sawynok, J. (1989) GABAergic agents as analgesics, in GABA: Basic Research and Clinical Applications ( Bowery, N. G. and Nistico, G., eds.), Pythagora, Rome, pp. 383–399.

    Google Scholar 

  • Schousboe, A., Diemer, N. H., and Kofod, H. eds. (1992a) Drug Research Related to Neuroactive Amino Acids,Munksgaard, Copenhagen.

    Google Scholar 

  • Schousboe, A., Hansen, G. H., and Belhage, B. (1992b) Regulation of neurotransmitter release by GABAA receptors in glutamatergic neurons, in New Leads and Targets in Drug Research ( Krogsgaard-Larsen, P., Christensen, S. B., and Kofod, H., eds.), Munksgaard, Copenhagen, pp. 176–186.

    Google Scholar 

  • Schousboe, A., Larsson, O. M., Hertz, L., and Krogsgaard-Larsen, P. (1981) Heterocyclic GABA analogues as new selective inhibitors of astroglial GABA transport. Drug Dev. Res. 1, 115–127.

    CAS  Google Scholar 

  • Schousboe, A., Thorbek, P., Hertz, L., and Krogsgaard-Larsen, P. (1979) Effects of GABA analogues of restricted conformation on GABA transport in astrocytes and brain cortex slices and on GABA receptor binding. J. Neurochem. 33, 181–189.

    Google Scholar 

  • Serra, M., Foddi, M. C., Ghiani, C. A., Melis, M. A., Motzo, C., Concas, A., Sanna, E., and Biggio, G. (1992) Pharmacology of y-aminobutyric acid, receptor complex after the in vivo administration of the anxioselective and anticonvulsant f3-carboline derivative abecarnil. Pharmacol. Exp. Ther. 263, 1360–1368.

    Google Scholar 

  • Sieghart, W. (1992) GABA, receptors: ligand-gated Cl— ion channels modulated by multiple drug-binding sites. Trends Pharmacol. Sci. 13, 446–450.

    PubMed  CAS  Google Scholar 

  • Sieghart, W. (1995) Structure and pharmacology of y-aminobutyric acid, receptor subtypes. Pharmacol. Rev. 47, 181–234.

    PubMed  CAS  Google Scholar 

  • Sieghart, W., Eichinger, A., Richards, J. G., and Möhler, H. (1987) Photoaffinity labeling of benzodiazepine receptor proteins with the partial inverse agonist [3H]Ro 15–4513: a biochemical and autoradiographic study. J. Neurochem. 48, 46–52.

    PubMed  CAS  Google Scholar 

  • Sivilotti, L. and Nistri, A. (1991) GABA inhibits neuronal activity by activating GABAB receptors coupled to K* channels. Prog. Neurobiol. 36, 35–92.

    PubMed  CAS  Google Scholar 

  • Smith, G. B. and Olsen, R. W. (1995) Functional domains of GABA, receptors. Trends Pharmacol. Sci. 16, 162–168.

    PubMed  CAS  Google Scholar 

  • Solimena, M. and De Camilli, P. (1993) Spotlight on a neuronal enzyme. Nature 366, 15–17.

    Google Scholar 

  • Squires, R. F. and Braestrup, C. (1977) Benzodiazepine receptors in rat brain. Nature 266, 732–734.

    PubMed  CAS  Google Scholar 

  • Squires, R. F., Lajtha, A., Saederup, E., and Palkovits, M. (1993) Reduced [3H]flunitrazepam binding in cingulate cortex and hippocampus of post mortem schizophrenic brains: is selective loss of glutamatergic neurons associated with major psychoses. Neurochem. Res. 18, 219–223.

    PubMed  CAS  Google Scholar 

  • Squires, R. F. and Saederup, E. (1991) A review of evidence for GABAergic predominance/glutamertergic deficit as a common etiological factor in both schizophrenia and affective psychoses: more support for a continuum hypothesis of“functional” psychosis. Neurochem. Res. 16, 1099–1111.

    PubMed  CAS  Google Scholar 

  • Stone, T. W. (1979) Glutamate as the neurotransmitter of cerebellar granule cells in the rat: electrophysiological evidence. Br. J. Pharmacol. 66, 291–296.

    PubMed  CAS  Google Scholar 

  • Supavilai, P. and Karobath, M. (1985) Modulation of acetylcholine release from rat striatal slices by the GABA/benzodiazepine receptor complex. Life Sci. 36, 417–426.

    PubMed  CAS  Google Scholar 

  • Tallman, J. F., Paul, S. M., Skolnick, P., and Gallager, D. W. (1980) Receptors for the age of anxiety: pharmacology of the benzodiazepines. Science 207, 274–281.

    PubMed  CAS  Google Scholar 

  • Tamminga, C. A., Crayton, J. W., and Chase, T. N. (1978) Muscimol: GABA agonist therapy in schizophrenia. Am. J. Psychiat. 135, 746–747.

    PubMed  CAS  Google Scholar 

  • Tamminga, C. A., Crayton, J. W., and Chase, T. N. (1979) Improvement of tardive dyskinesia after muscimol therapy. Arch. Gen. Psychiat. 36, 595–598.

    PubMed  CAS  Google Scholar 

  • Thaker, G. K., Hare, T. A., and Tamminga, C. A. (1983) GABA system: clinical research and treatment of tardive dyskinesia. Mod. Probi. Pharmacopsychiat. 21, 155–167.

    CAS  Google Scholar 

  • Thaker, G. K., Nguyen, J. A., and Tamminga, C. A. (1989) Increased saccadic distractability in tardive dyskinesia: functional evidence for subcortical GABA dysfunction. Biol. Psychiatry 25, 49–59.

    PubMed  CAS  Google Scholar 

  • Theobald, W., Buch, O., Kunz, H. A., Krupp, P., Stenger, E. G., and Heimann, H. (1968) Pharmakologische und experimentalpsychologische untersuchungen mit 2 inhaltsstoffen des fliegenpilzes (amanita muscaria). Arzneim. Forsch. 18, 311–315.

    CAS  Google Scholar 

  • Tirsch, R., Yang, X.-D., Singer, S. M., Liblau, R. S., Fugger, L., and McDevitt, H. O. (1993) Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature 366, 72–75.

    Google Scholar 

  • Travagli, R. A., Ulivi, M., and Wojcik, W. J (1991) y-Aminobutyric acid-B receptors inhibit glutamate release from cerebellar granule cells: consequences of inhibiting cyclic AMP formation and calcium influx. J. Pharm. Exp. Ther. 258, 903–909.

    Google Scholar 

  • Usami, S., Hozawa, J., Tazawa, M., Igarashi, M., Thompson, G. C., Wu, J. Y., and Wenthold, R. J. (1989) Immunocytochemical study of the GABA system in chicken vestibular endorgans and the vestibular ganglion. Brain Res. 503, 214–218.

    PubMed  CAS  Google Scholar 

  • Van Ness, P. C., Watkins, A. E., Bergman, M. O., Tourtelotte, W. W., and Olsen, R. W. (1982) y-Aminobutyric acid receptors in normal human brain and Huntington’s disease. Neurology 32, 63–68.

    Google Scholar 

  • Venault, P., Chapouthier, G., Prado de Carvalho, L., Simiand, J., Morre, M., Dodd, R. H., and Rossier, J. (1986) Benzodiazepine impairs and f 3-carboline enhances performance in learning and memory tasks. Nature 321, 864–866.

    PubMed  CAS  Google Scholar 

  • Verdoorn, T. A., Draguhn, A., Ymer, S., Seeburg, R. H., and Sakmann, B. (1990) Functional properties of recombinant rat GABAA receptors depend upon subunit composition. Neuron 4, 919–928.

    PubMed  CAS  Google Scholar 

  • Virmani, M. A., Stojilkovic, S. S., and Catt, K. J. (1990) Stimulation of luteinizing hormone release by y-aminobutyric acid (GABA) agonists: mediation by GABAA-type receptors and activation of chloride and voltage-sensitive calcium channels. Endocrinology 126, 2499–2505.

    PubMed  CAS  Google Scholar 

  • Walton, M. K., Schaffner, A. E., and Barker, J. L. (1993) Sodium channels, GABAA receptors, and glutamate receptors develop sequentially on embryonic rat spinal cord cells. J. Neurosci. 13, 2068–2084.

    PubMed  CAS  Google Scholar 

  • Wermuth, C. G. and Biziére, K. (1986) Pyridazinyl-GABA derivatives: a new class of synthetic GABAA antagonists. Trends Pharmacol. Sci. 7, 421–424.

    CAS  Google Scholar 

  • Wermuth, C. G., Bourguignon, J.-J., Schlewer, G., Gies, J.-P., Schoenfelder, A., Melikian, A., Bouchet, M.-J., Chantreux, D., Molimard, J.-C., Heaulme, M., Chambon, J.-P., and Biziére, K. (1987) Synthesis and structure-activity relationships of a series of aminopyridazine derivatives of y-aminobutyric acid acting as selective GABA-A antagonists. J. Med. Chem. 30, 239–249.

    Google Scholar 

  • Wheal, H. and Thomson, A., eds. (1995) Excitatory Amino Acids and Synaptic Transmission, 2nd ed, Academic, London.

    Google Scholar 

  • Wieland, H. A., Luddens, H., and Seeburg, R. H. (1992) A single histidine in GABAA receptors is essential for benzodiazepine agonist binding. J. Biol. Chem. 267, 1426–1429.

    PubMed  CAS  Google Scholar 

  • Woodward, R. M., Polenzani, L., and Miledi, R. (1993) Characterization of bicuculline/ baclofen-insensitive (r-like) y-aminobutyric acid receptors expressed in Xenopus oocytes. II. Pharmacology of y-aminobutyric acidA and y-aminobutyric acidB receptor agonists and antagonists. Mol. Pharmacol. 43, 609–625.

    PubMed  CAS  Google Scholar 

  • Wurtman, R. J., Corkin, S., Growdon, J. H., and Ritter-Walker, E., eds. (1990) Advances in Neurology, vol. 51. Alzheimer’s Disease, Raven, New York.

    Google Scholar 

  • Zhang, P., Zhang, W., Liu, R., Harris, B., Skolnick, P., and Cook, J. M. (1995) Synthesis of novel imidazobenzodiazepines as probes of the pharmacophore for “diazepam-insensitive” GABAA receptors. J. Med. Chem. 38, 1679–1688.

    PubMed  CAS  Google Scholar 

  • Zorn, S. H. and Enna, S. J. (1987) The GABA agonist THIP attenuates antinociception in the mouse by modifying central cholinergic transmission. Neuropharmacology 26, 433–437.

    PubMed  CAS  Google Scholar 

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  1. Povl Krogsgaard-Larsen
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  2. Bente Frølund
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  1. Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical School, Kansas City, KS, USA

    S. J. Enna

  2. Department of Pharmacology, The Medical School Edgbaston, University of Birmingham, UK

    Norman G. Bowery

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Krogsgaard-Larsen, P., Frølund, B., Ebert, B. (1997). GABAA Receptor Agonists, Partial Agonists, and Antagonists. In: Enna, S.J., Bowery, N.G. (eds) The GABA Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2597-1_3

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