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Pharmacology of Mammalian GABAA Receptors

  • Chapter
The GABA Receptors

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

Abstract

γ-Aminobutyric acid (GABA) is the most prevalent neurotransmitter in the mammalian brain and exerts its main actions through GABAA receptors (GABAARs). GABAARs have proven to serve as the primary target for many important neuroactive drugs, including benzodiazepines (BZs), barbiturates, steroids, general anesthetics, and possibly ethanol (Macdonald and Olsen, 1994). Recent elegant studies of the molecular nature of GABAARs have revealed the existence of multiple subtypes of these receptors, the composition of which is determined by the formation of pentameric structures from members of at least three distinct subunit families (αl–6, β1–3, γl–3) (Lüddens et al., 1995). Furthermore, by using sophisticated in vitro techniques, the regulation of functional properties by GABA itself, as well as other modulators of GABAARs, has now been shown to differ dramatically with the type of subunit variants in the pentameric complex (Lüddens et al., 1995; Sieghart, 1995).

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References

  • Allan, A. M., Baier, L. D., and Zhang, X. (1992) Effects of lorazepam tolerance and withdrawal on GABAA receptor-operated chloride channels. J Pharmacol. Exp. Ther. 261, 295–402.

    Google Scholar 

  • Angelotti, T. and Macdonald, R. L. (1993) Assembly of GABAA receptor subunits: a,ß, and a, 0,72s subunits produce unique ion channels with dissimilar single-channel properties. J. Neurosci. 13, 1429–1440.

    PubMed  CAS  Google Scholar 

  • Anholt, R. R., De Souza, E. B., Oster-Granite, M. L., and Snyder, S. H. (1985) Peripheral-type benzodiazepine receptors: autoradiographic localisation in whole-body sections of neonatal rats. J Pharmacol. Exp. Ther. 233, 517–526.

    PubMed  CAS  Google Scholar 

  • Ansseau, M., Olie, J-P., Von Frenckell, R., Jourdain, G., Stehle, B., and Guillet, P. (1991) Controlled comparisons in the efficacy and safety of four doses of suriclone, diazepam and placebo in generalised anxiety disorder. Psychopharmacology 104, 439–443.

    Google Scholar 

  • Arbilla, S., Benavides, J., Scatton, B., Tan, S., and Langer, S. Z. (1993) The mechanism of action of alpidem, in Imidazopyridines and Anxiety Disorders: A Novel Experimental and Therapeutic Approach (Bartholini, G., Garreau, M., Morselli, P. L., and Zivkovic, B., eds.), Raven, New York, pp. 61–67.

    Google Scholar 

  • Arbilla, S., Depoortere, H., George, P., and Langer, S. Z. (1985) Pharmacological profile of zolpidem at benzodiazepine receptors and electrocorticogram in rats. Naunyn Schmiedeberg’s Arch. Pharmacol. 330, 248–251.

    PubMed  CAS  Google Scholar 

  • Auta, J., Giusti, P., Guidotti, A., and Costa, E. (1994) Imidazenil, a partial positive allosteric modulator of GABAA receptors, exhibits low tolerance and dependence liabilities in the rat. J. Pharmacol. Exp. Ther. 270, 1262–1269.

    Google Scholar 

  • Ballenger, J. C., McDonald, S., Noyes, R., Rickelo, K., Sussman, N., Woods, S., Patin, J., and Singer, J. (1991) The first double blind, placebo-controlled trial of a partial benzodiazepine agonist abecarnil (ZK 112–119) in generalised anxiety disorder. Psychopharmacol. Bull. 27, 171–179.

    Google Scholar 

  • Baulieu, E.-E., Robel, P., Vatier, O., Haug, A., Le Gascogne, C., and Bourreau, E. (1987) Neurosteroids: pregnenolone and dehydroepiandrosterone in the rat brain, in Receptor-Receptor Interaction, a New Intramembrane Integrative Mechanism ( Fuxe, K. and Agnati, L. F., eds.), MacMillan, Basingstoke, UK, pp. 89–104.

    Google Scholar 

  • Benavides, J., Peny, B., Dubois, A., Perrault, G., Morel, E., Zivkovic, B., and Scatton, B. (1987) In vivo interaction of zolpidem with central benzodiazepine (BZD) binding sites (as labeled by [3H]Ro 15–1788) in the mouse brain. Preferential affinity of zolpidem for the coi (BZD i)subtype. J. Pharmacol. Exp. Ther. 245, 1033–1041.

    Google Scholar 

  • Benavides, J., Peny, B., Ruano, D., Vitorica, J., and Scatton, B. (1993) Comparative autoradiographic distribution of central co (benzodiazepine) modulatory site subtypes with high, intermediate and low affinity for zolpidem and alpidem. Brain Res. 604, 240–250.

    PubMed  CAS  Google Scholar 

  • Blackburn, T. P., Davies, D. T., Forbes, I. T., Hayward, C. J., Johnson, C. N., Martin, R. T., Piper, D. C., Thomas, D. R., Thompson, M., Upton, N., and Ward, R. W. (1995) Isosteric replacement of the indole nucleus by benzothiophene in a series of pyrido[2,3b]indoles with potential anxiolytic activity. Bioorg. Med. Chem. Lett. 5 2589–2592.

    Google Scholar 

  • Blanchard, J. C., Boireau, A., Garret, C., and Julou, L. (1979) In vitro and in vivo inhibition by zopic lone of benzodiazepine binding to rodent brain receptors. Life Sci. 24, 2417–2420.

    CAS  Google Scholar 

  • Blanchard, J. C. and Julou, L. (1983) Suriclone—a new cyclopyrrolone derivative recognising receptors labelled by benzodiazepines in rat hippocampus and cerebellum. J. Neurochem. 40, 601–607.

    PubMed  CAS  Google Scholar 

  • Bormann, J. (1988) Electrophysiology of GABA, and GABA, receptor subtypes. Trends Neurosci. 11, 112–116.

    PubMed  CAS  Google Scholar 

  • Bowery, N. G., Collins, J. F., and Hill, R. G. (1976) Bicyclic phosphorous esters that are potent convulsants and GABA antagonists. Nature (Lond.) 261, 601–603.

    CAS  Google Scholar 

  • Braestrup, C. (1977) Benzodiazepine receptors in rat brain. Nature (Lond.) 266, 732–734.

    Google Scholar 

  • Braestrup, C. and Nielsen, M. (1983) Benzodiazepine receptors, in Handbook of Psychopharmacology, vol. 17 ( Iversen, L. L., Iversen, S. D., and Snyder, S. H., eds.),Plenum, New York, pp. 285–384.

    Google Scholar 

  • Braestrup, C., Nielsen, M., Honore, T., Jensen, I. H., and Petersen, E. N. (1983) Benzodiazepine receptor ligands with positive and negative efficacy. Neuropharmacology 22, 1451–1457.

    PubMed  CAS  Google Scholar 

  • Braestrup, C., Nielsen, M., and Olsen, C. E. (1980) Urinary and brain ß-carboline- 3-carboxylates as potent inhibitors of brain benzodiazepine receptors. Proc. Natl. Acad. Sci. USA 77, 2288–2292.

    PubMed  CAS  Google Scholar 

  • Braestrup, C., Schmeichen, R., Neef, G., Nielsen, M., and Petersen, E. N. (1982) Interaction of convulsive ligands with benzodiazepine receptors. Science (Wash., DC) 216, 1241–1243.

    CAS  Google Scholar 

  • Brogden, R. N. and Goa, K. L. (1991) Flumazenil: a reappraisal of its pharmacological properties and therapeutic efficacy as a benzodiazepine antagonist. Drugs 42, 1061–1089.

    PubMed  CAS  Google Scholar 

  • Brooks-Kayal, A. R. and Pritchett, D. B. (1993) Developmental changes in human y- aminobutyric acid, receptor subunit composition. Annals of Neurol. 34, 687–693.

    CAS  Google Scholar 

  • Busto, U., Kaplan, H. L., Zawertailo, L., and Sellers, E. M. (1994) Pharmacologic effects and abuse liability ofbretazenil, diazepam and alprazolam in humans. Clin. Pharmacol. Ther. 55, 451–463.

    PubMed  CAS  Google Scholar 

  • Callachan, H. Cottrell, G. A., Hather, N. Y., Lambert, J. J. Nooney, J. M., and Peters, J. A. (1987) Modulation of the GABA, receptor by progesterone metabolites. Proc. R. Soc. London Ser. 231 359–369.

    Google Scholar 

  • Charney, D.S. and Woods, S.W. (1989) Benzodiazepine treatment of panic disorder: a comparison of alprazolam and lorazepam. J. Clin. Psychiatry 50, 418–423.

    PubMed  CAS  Google Scholar 

  • Chevalier, S. F., Mendelwicz, J., and Coupez, R. (1993) Safety and efficacy of alpidem, in Imidazopyridines in Anxiety Disorders: A Novel Experimental and Therapeutic Appraoch ( Bartholini, G., Garreau, M., Morselli, P.L., and Zivkovic, B., eds.), Raven, New York, pp. 193–199.

    Google Scholar 

  • Concas, A., Serra, M., Atsoggiu, T., and Biggio, G. (1988) Foot-shock stress and anxiogenic ß-carbolines increase t35S]butylbicyclophosphorothionate binding in the rat cerebral cortex, an effect opposite to anxiolytic and y-aminobutyric acid mimetics. J. Neurochem. 51, 1868–1876.

    PubMed  CAS  Google Scholar 

  • Concas, A., Serra, M., Santoro, G., Maciocco, E., Cuccheddu, T., and Biggio, G. (1994) The effect of cyclopyrrolones on GABAA receptor function is different from that of benzodiazepines. Naunyn Schmiedebergs Arch. Pharmacol. 350, 294–300.

    Google Scholar 

  • Costa, E. and Guidotti, A. (1991) Minireview: diazepam binding inhibitor (DBI): a peptide with multiple biological actions. Life Sci. 49, 325–344.

    PubMed  CAS  Google Scholar 

  • Costa, E., Guidotti, A., Mao, C. C., and Suria, A. (1975) New concepts on the mechanism of action of the benzodiazepines. Life Sci. 17, 167–186.

    PubMed  CAS  Google Scholar 

  • Depoortere, B., Zivkovic B., Lloyd, K. G., Sanger, D. J., Perrault, G., Langer, S. Z., and Bartholini, G. (1986) Zolpidem, a novel nonbenzodiazepine hypnotic. I. Neuro-pharmacological and behavioural effects. J. Pharmacol. Exp. Ther. 237, 649–658.

    PubMed  CAS  Google Scholar 

  • Dillon, G. H., Im, W. B., Carter, D. B., and McKinley, D. D. (1995) Enhancement by GABA of the association rate ofpicrotoxin and tert-butylbicyclophosphorothionate to the rat cloned a,ß2y2 GABAA receptor subtype. Br. J. Pharmacol. 115, 539–545.

    PubMed  CAS  Google Scholar 

  • Dillon, G. H., Im, H. K., Hamilton, B. J., Carter, D. B., Gammill, R. B., Judge, T. M., and Im, W. B. (1993) U-93631 causes rapid decay of y-aminobutyric acid-induced chloride currents in recombinant rat y-aminobutyric acid type A receptors. Mol. Pharmacol. 44, 860–864

    PubMed  CAS  Google Scholar 

  • Doble, A., Canton, T., Malgouris, C., Stutzmann, J. M., Piot, O., Bardone, M. C., Pauchet, C., and Blanchard, J. C. (1995) The mechanism of action ofzopiclone. Eur. Psychiatry 10 (Suppl. 3) 117–128.

    Google Scholar 

  • Doble, A., Canton, T., Piot, O., Zundel, J. L., Stutzmann, J. M., Cotrel, C., and Blanchard, J. C. (1992) The pharmacology of cyclopyrrolone derivatives acting at the GABAA/ benzodiazepine receptors, in GABAergic Synaptic Transmission: Molecular, Pharmacological and Clinical Aspects ( Biggio, G., Concas, A., and Costa, E., eds.), Raven, New York, pp. 407–418.

    Google Scholar 

  • Dorow, R., Horowski, R., Paschelke, G., Amin, M., and Braestrup, C. (1983) Severe anxiety induced by FG 7142, a 3-carboline ligand for benzodiazepine receptors. Lancet II, 98–99.

    Google Scholar 

  • Dubois, A., Benavides, J., Peny, B., Duverger, D., Fage, D., Gotti, B., MacKenzie, E. T., and Scatton, B. (1988) Imaging of primary and remote ischaemic and excitotoxic brain lesions. An autoradiographic study of peripheral type benzodiazepine binding sites in the rat and cat. Brain Res. 445, 77–90.

    PubMed  CAS  Google Scholar 

  • Duncan, G. E., Breese, G. R., Criswell, H. E., McCowan, T. J., Herbert, J. S., Devaud, L. L., and Morrow, A. L. (1995) Distribution of [3H]zolpidem binding sites in relation to messenger RNA encoding the a1, ß2 and y2 subunits of GABAA receptors in rat brain. Neuroscience 64, 1113–1128.

    PubMed  CAS  Google Scholar 

  • Edgar, P. P. and Schwarz, R. D. (1992) Functionally relevant y-aminobutyric acidA receptors: equivalence between receptor affinity (Ks) and potency (EC„)? Mol. Pharmacol. 41, 1124–1129.

    CAS  Google Scholar 

  • Facklam, M., Schoch, P., Bonetti, E. P., Jenck, F., Martin, J. R., Moreau, J. L., and Haefely, W. E. (1992a) Relationship between benzodiazepine receptor occupancy and functional effects in vivo of four ligands of differing intrinsic efficacies. J. Pharmacol. Exp. Ther. 261, 1113–1121.

    PubMed  CAS  Google Scholar 

  • Facklam, M., Schoch, P., and Haefely, W. (1992b) Relationship between benzodiazepine receptor occupancy and potentiation of y-aminobutyric acid-stimulated chloride flux in vitro of four ligands of differing intrinsic efficacies. J. Pharmacol. Exp. Ther. 261, 1106–1112.

    PubMed  CAS  Google Scholar 

  • Faure-Halley, C., Graham, D., Arbilla, S., and Langer, S. Z. (1993) Expression and properties of recombinant 0272 and a5132y2 forms of the rat GABAA receptor. Eur. J. Pharamacol. 246, 283–287.

    CAS  Google Scholar 

  • File, S.E. (1985) Tolerance to the behavioural actions of benzodiazepines. Neurosci. Biobehay. Rev. 9, 113–122.

    CAS  Google Scholar 

  • File, S. E. and Pellow, S. (1987) Behavioural pharmacology of minor tranquilisers. Pharmac. Ther. 35, 265–290.

    CAS  Google Scholar 

  • Forster, M. J., Prather, P. L., Patel, S. R., and Lal, H. (1995) The benzodiazepine receptor inverse agonist RO 15–3505 reverses recent memory deficits in aged mice. Pharmacol. Biochem. Behan 51, 557–560.

    Google Scholar 

  • Fritschy, J. M., Paysan, J., Enna, A., and Möhler, H. (1994) Switch in the expression of rat GABAA-receptor subtypes during postnatal development: an immunohistochemical study. J. Neurosci. 14, 5302–5324.

    PubMed  CAS  Google Scholar 

  • Fuchs, K., Möhler, H., and Sieghart, W. (1988) Various proteins from rat brain, specifically and irreversibly labeled by [3H]flunitrazepam, are distinct a-subunits of the GABA benzodiazepine receptor complex. Neurosci. Lett. 90, 314–319.

    PubMed  CAS  Google Scholar 

  • Gallager, D. W., Lakoski, J. M., Gonsales, S. F., and Rauch, S. L. (1984) Chronic benzo- diazepine treatment decreases postsynaptic GABA sensitivity. Nature 308, 74–77.

    PubMed  CAS  Google Scholar 

  • Gardner, C. R. (1989) Interpretation of the behavioural effects of benzodiazepine receptor ligands. Drugs of the Future 14, 51–67.

    Google Scholar 

  • Gee, K.W. (1988) Steroid modulation ofthe GABA/benzodiazepine receptor linked chloride ionophore. Mol. Neurobiol. 2, 291–317.

    PubMed  CAS  Google Scholar 

  • Gee, K. W., Lawrence, L. J., and Yamamura, H. J. (1986) Modulation of the chloride ionophore by benzodiazepine receptor ligands: influence of y-aminobutyric acid and ligand efficacy. Mol. Pharmacol. 30, 218–225.

    PubMed  CAS  Google Scholar 

  • Gee, K. W., McCauley, L. D., and Lan, N. C. (1995) A putative receptor for neurosteroids on the GABAA receptor complex: the pharmacological properties and therapeutic potential of epalons. Crit. Rev. Neurobiol. 9, 207–227.

    Google Scholar 

  • Gillard, N. R, Quirk K., Ragan, C. I., and McKernan, R. M. (1991) [125I]Iodoclonazepam, a specific high affinity radioligand for the identification of BZ1 and BZ2 sites in rat brain. Eur. J. Pharmacol. 195, 407–409.

    Google Scholar 

  • Giusti, P. and Arban, R. (1993) Physiological and pharmacological bases for the diverse properties of benzodiazepines and their congeners. Pharmacol. Res. 27, 201–215.

    PubMed  CAS  Google Scholar 

  • Giusti, P., Ducic, I., Puia, G., Arban, R., Walser, A., Guidotti, A., and Costa, E. (1993) Imidazenil: a new partial positive allosteric modulator ofy-aminobutyric acid (GABA) action at GABAA receptors. J. Pharmacol. Exp. Ther. 266, 1018–1028.

    PubMed  CAS  Google Scholar 

  • Givens, B. S. and Breese, G. R. (1990) Site-specific enhancement of y-aminobutyric acid mediated inhibition of neural activity by ethanol in the rat medial septal area. J. Pharmacol. Exp. Ther. 254, 528–538.

    PubMed  CAS  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 Lüscher, B. (1995) Benzodiazepine-insensitive mice generated by targeted disruption of the y2 subunit gene ofy-aminobutyric acid type A receptors. Proc. Natl. Acad. Sci. 92, 7745–7753.

    Google Scholar 

  • Haefely, W. (1989) Pharmacology of the allosteric modulation of GABAA receptors by benzodiazepine receptor ligands, in Allosteric Modulation of Amino Acid Receptors: Therapeutic Implications ( Barnard, E. A., and Costa, E., eds.), Raven, New York, pp. 47–69.

    Google Scholar 

  • Haefely, W., Bonetti, E. P., Burkard, W. P., Cumin, R., Laurent, J.-P., Möhler, H., Pieri, L., Polc, P., Richards, J. G., Schaffner, R., and Scherschlicht, R. (1983) Benzodiazepine antagonists, in The Benzodiazepines: From Molecular Biology to Clinical Practice (Costa, E., ed.), Raven, New York, pp. 137–146.

    Google Scholar 

  • Haefely, W., Kuskar, A., Möhler, H., Pieri, L., Polc, P., and Schaffner, R. (1975) Possible involvement of GABA in the central actions of benzodiazepines. Adv. Biochem. Psychopharmacol. 14, 131–152.

    PubMed  CAS  Google Scholar 

  • Haefely, W., Kyburz, E., Gerecke, M., and Möhler, H. (1985) Recent advances in the molecular pharmacology of benzodiazepine receptors and in the structure-activity relationships of their agonists and antagonists, in Advances in Drug Research, vol. 14 ( Testa, B., ed.) Academic, London, pp. 165–322.

    Google Scholar 

  • Haefely, W., Martin, J. R., and Schoch, P. (1990) Novel anxiolytics that act as partial agonists at benzodiazepine receptors. Trends Pharmacol. Sci. 11, 452–456.

    Google Scholar 

  • Haigh, J. R. M. and Freely, M. (1988) RO 16–6028, a benzodiazepine receptor partial agonist, does not exhibit anticonvulsant tolerance in mice. Eur. J. Pharmacol. 147, 283–285.

    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 

  • Henry, T. R., Frey, K. A., Sakellares, J. C., Gilman, S., Koeppe, R. A., Brunberg, J. A., Ross, D. A., Berent, S., Young, A. B., and Kuhl, D. E. (1993) In vivo cerebral metabolism and central benzodiazepine-binding in temporal lobe epilepsy. Neurology 43 1998–2006.

    Google Scholar 

  • Hobbs, R. W., Rall, T. W., and Verdon, T. A. (1996) Hypnotics and sedatives; ethanol, in Goodman and Gilman ‘s The Pharmacological Basis of Therapeutics, 9th ed. ( Hardman, J. G. and Limbard, L. E., eds.), McGraw-Hill, New York, pp. 361–396.

    Google Scholar 

  • Hollister, L. E., Muller-Oerlinghausen, B., Rickels, K., and Shader, R. I. (1993) Clinical use of benzodiazepines. J. Clin. Psychopharmacol. 13 (Suppl. 1) 1–169.

    Google Scholar 

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

    CAS  Google Scholar 

  • Im, W. B. and Blakeman, D. P. (1991) Correlation between y-aminobutyric acidA receptor ligand-induced changes in t-butylbicyclophosphoro-[35S]thionate binding and 36C1-uptake in rat cerebrocortical membranes. Mol. Pharmacol. 39, 394–398.

    Google Scholar 

  • Inomata, N., Tokutomi, N., Oyama, Y., and Akaike, N. (1988) Intracellular picrotoxin blocks pentobarbital-gated Cl-conductance. Neurosci. Res. 6, 72–75.

    PubMed  CAS  Google Scholar 

  • Jensen, L. H., Stephens, D. N., Satter, M., and Petersen, E. N. (1987) Bidirectional effects of ß-carbolines and benzodiazepines on cognitive processes. Brain Res. Bull. 19, 359–364.

    PubMed  CAS  Google Scholar 

  • Jones, G. H., Schneider, C., Schneider, H. H., Seidler, J., Cole, B. J., and Stephens, D. N. (1994) Comparison of several benzodiazepine receptor ligands in two models of anxiolytic activity in the mouse: an analysis based on fractional receptor occupancies. Psychopharmacology 114, 191–199.

    PubMed  CAS  Google Scholar 

  • Julou, L., Blanchard, J. C., and Dreyfus, J. F. (1985) Pharmacological and clinical studies of cyclopyrrolones: zopiclone and suriclone. Pharmacol. Biochem. Behay. 23, 653–659.

    CAS  Google Scholar 

  • Kardos, J. and Cash, D. J. (1990) 36C1- flux measurements and desensitization of the y-aminobutyric acid, receptor. J. Neurochem. 55, 1095–1099.

    Google Scholar 

  • Karobath, M., Placheta, P., Lippitsch, M., and Krogsgaard-Larsen, P. (1979) Is stimulation of benzodiazepine receptor binding mediated by a novel GABA receptor? Nature (Lond.) 278, 748, 749.

    Google Scholar 

  • Kerr, J. S., Dawe, R. A., Parkin, C., and Hindmarch, I. (1995) Zopiclone in elderly patients: efficacy and safety. Human Psychopharmacol. 10, 221–229.

    Google Scholar 

  • Klepner, C. A., Lippa, A. S., Benson, D. I., Sabo, M. C., and Beer, B. (1979) Resolution of two biochemically and pharmacologically distinct benzodiazepine receptors. Pharmacol. Biochem. Behay. 11, 457–462.

    Google Scholar 

  • Knoflach, F., Drescher, U., Scheurer, L., Malherbe, P., and Möhler, H. (1993) Full and partial agonism displayed by benzodiazepine receptor ligands at recombinant y-aminobutyric acid, receptor subtypes. J. Pharmacol. Exp. Ther. 266, 385–391.

    PubMed  CAS  Google Scholar 

  • Korpi, E.R. (1994) Role of GABA, receptors in the actions of alcohol and alcoholism: recent advances. Alcohol and Alcoholism 29, 115–129.

    PubMed  CAS  Google Scholar 

  • Lader, M. H. (1993) Withdrawal symptoms and rebound with anxiolytic drugs, in Imidazopyridines in Anxiety Disorders: A Novel Experimental and Therapeutic Appraoch ( Bartholini, G., Garreau, M., Morselli, P. L., and Zivkovic, B., eds.), Raven, New York, pp. 227–233.

    Google Scholar 

  • Lader, M. H. (1994) Benzodiazepines: a risk-benefit profile. CNS Drugs 1, 377–387.

    Google Scholar 

  • Lader, M. H. and File, S. H. (1987) The biological basis of benzodiazepine dependence. Psychological Med. 17, 593–547.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Lan, N. C. and Gee, K. W. (1991) GABA, receptor complex in rat frontal cortex and spinal cord show differential responses to steroid modulation. Am. Soc. Pharm. Exp. Ther. Mol. Pharmacol. 40, 995–999.

    Google Scholar 

  • Langer, S. Z. and Arbilla, S. (1988a) Limitations of the benzodiazepine receptor nomenclature: a proposal for a pharmacological classification as omega receptor subtypes. Fund. Clin. Pharmacol. 2, 159–170.

    CAS  Google Scholar 

  • Langer, S. Z. and Arbilla, S. (1988b) Imidazopyridines as a tool for the charactersiation of benzodiazepine receptors: a proposal for a pharmacological classification as omega receptors. Pharmacol. Biochem. Behay. 29, 763–766.

    CAS  Google Scholar 

  • Langtry, H. D. and Benfield, P. (1990) Zolpidem. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential. Drugs 40, 291–313.

    PubMed  CAS  Google Scholar 

  • Legris, P., George, Y., and Boval, P. (1993) A comparative study of alpidem versus buspirone, in Imidazopyridines in Anxiety Disorders: A Novel Experimental and Therapeutic Appraoch ( Bartholini, G., Garreau, M., Morselli, P.L., and Zivkovic, B., eds.) Raven, New York, pp. 183–192.

    Google Scholar 

  • Leonard, B. E. (1993) Commentary on the mode of action of benzodiazepines. J. Psychiatr. Res. 27 (Suppl. 1) 193–207.

    Google Scholar 

  • Lippa, A. S., Coupet, J., Greenblatt, E. N., Klepner, C. A., and Beer, B. (1979) A synthetic nonbenzodiazepine ligand for benzodiazepine receptors: a probe for investigating neuronal substrates of anxiety. Pharmacol. Biochem. Behay. 11, 99–106.

    CAS  Google Scholar 

  • Little, H. J., Nutt, D. J., and Taylor, S. C. (1984) Acute and chronic effects of benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling. Br. J. Pharmacol. 83, 951–958.

    PubMed  CAS  Google Scholar 

  • Löscher, W. (1993) Abecarnil shows reduced tolerance development and dependence potential in comparison to diazepam: animal studies. Psychopharmacol. Ser. 11, 96–112.

    PubMed  Google Scholar 

  • Löscher, W., Hönack, D., Scherkl, R., Hashem, A., and Frey, H. H. (1990) Pharmacokinetics, anticonvulsant efficacy and adverse effects of the ß-carboline abecarnil, a novel ligand for benzodiazepine receptors, after acute and chronic administration in dogs. J. Pharmacol. Exp. Ther. 225, 541–548.

    Google Scholar 

  • Löscher, W. and Schmidt, D. (1988) Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations. Epilepsy Res. 2, 145–181.

    PubMed  Google Scholar 

  • Lüddens, H. and Korpi, E. R. (1995) Biological function of GABAA/benzodiazepine receptor heterogeneity. J. Psychiat. Res. 29, 77–94.

    PubMed  Google Scholar 

  • Lüddens, H., Korpi, E. R., and Seeburg, P. H. (1995) GABAA/benzodiazepine receptor heterogeneity: neurophysiological implications. Neuropharmacology 34, 245–254.

    PubMed  Google Scholar 

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

    Google Scholar 

  • Lüddens, H., Seeburg, P. H., and Korpi, E. R. (1994) Impact of ß and y variants on ligand binding properties of y-aminobutyric acid type A receptors. Mol. Pharmacol. 45, 810–814.

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Macdonald, R. L. and Twyman, R. E. (1992) Kinetic properties and regulation of GABAA receptor channels, in Ion Channels, vol. 3 ( Narahashi, T., ed.), Plenum, New York, pp. 315–343.

    Google Scholar 

  • Majewska, M. D. (1992) Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance. Prog. Neurobiol. 38, 379–395.

    PubMed  CAS  Google Scholar 

  • Malgouris, C., Perrot, F., Dupuis, M., Kiosseff, T., Daniel, M., Blanchard, J. C., and Doble, A. (1995) Autoradiographic distribution of [3H]-suriclone binding sites in rat brain. Drug Dey. Res. 34, 336–343.

    CAS  Google Scholar 

  • Malizia, A. L. and Nutt, D. J. (1995) The effects of flumazenil in neuropsychiatrie disorders. Clin. Neuropharmacol. 3, 215–232.

    Google Scholar 

  • Marks, J. (1983) The benzodiazepines—for good or evil. Neuropsychobiology 10, 115–126.

    PubMed  CAS  Google Scholar 

  • McKernan, R. M. and Whiting, P. J. (1996) Which GABAA-receptor subtypes really occur in the brain. Trends Neurosci. 19, 139–143.

    PubMed  CAS  Google Scholar 

  • Miller, L. G., Greenblatt, D. J., Barnhill, J. G., and Shader, R. I. (1988) Tolerance is associated with benzodiazepine receptor down-regulation and decreased y-aminobutyric acidA receptor function. J. Pharmacol. Exp. Ther. 246, 170–176.

    PubMed  CAS  Google Scholar 

  • Miller, L. G., Woolverton, S., Greenblatt, D. J., Lopez, F., Roy, R. B., and Shader, R. I. (1989) Chronic benzodiazepine administration. IV. Rapid tolerance and receptor down regulation associated with alprazolam administration. Biochem. Pharmacol. 38, 3773–3777.

    Google Scholar 

  • Mindus, P., Ehrin, E., Eriksson, L., Fardre, L., and Hedstrom, C. G. (1986) Central benzodiazepine receptor binding studies with 1 IC labelled Ro 15–1788 and positron emission tomography. Pharmacopsychiatry 19, 2, 3.

    Google Scholar 

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

    Google Scholar 

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

    PubMed  Google Scholar 

  • Möhler, H. and Richards, J. G. (1981) Agonist and antagonist benzodiazepine receptor interaction in vitro. Nature (Lond.) 294, 763–765.

    Google Scholar 

  • Mukhin, A. G., Papadopoulos, V., Costa, E., and Krueger, K. E. (1989) Mitochondrial benzodiazepine receptors regulate steroid biosynthesis. Proc. Natl. Acad. Sci. USA 86, 9813–9816.

    PubMed  CAS  Google Scholar 

  • Mumford, G. K., Rush, C. R., and Griffiths, R. R. (1995) Abecarnil and alprazolam in humans: behavioural, subjective and reinforcing effects. J. Pharmacol. Exp. Ther. 272, 570–580.

    Google Scholar 

  • Musch, B. and Maillard, F. (1990) Zopiclone, the third generation hypnotic: a clinical overview. Int. Clin. Psychopharmacol. 5, 147–158.

    PubMed  Google Scholar 

  • Nutt, D. J., Smith, C. F., Bennett, R., and Jackson, H. C. (1992) Investigations on the “set-point” theory of benzodiazepine receptor function, in GABAergic Synaptic Transmission (Biggio, G., Concas, A., and Costa, E., eds.), Raven, New York, pp. 419–429.

    Google Scholar 

  • Obata, T., Morelli, M., Concas, A., Serra, M., andYamamura, H. I. (1988) Modulation of GABA-stimulated chloride flux into membrane vesicles from rat cerebral cortex by benzodiazepines and nonbenzodiazepines, in Chloride Channels and Their Modulation by Neurotransmitters and Drugs ( Biggio, G. and Costa, E., eds.), Raven, New York, pp. 175–187.

    Google Scholar 

  • O’Brien, C.P. (1996) Drug addiction and drug abuse, in Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. ( Hardman, J. G., and Limbard, L. E., eds.), McGraw-Hill, New York, pp. 557–577.

    Google Scholar 

  • Olsen, R.W. (1982) Drug interactions at the GABA receptor-ionophore complex. Ann. Rev. Pharmacol. Toxicol. 22, 245–277.

    CAS  Google Scholar 

  • Olsen, R. W., Bergmann, M. O., Van Ness, P. C., Lummis, S. C., Watkins, A. E., Napias, C., and Greenlee, D. V. (1981) 7-Aminobutyric acid receptor binding in mammalian brain. Heterogeneity of binding sites. Mol. Pharmacol. 19, 217–227.

    Google Scholar 

  • Olsen, R. W. and Snowman, A. M. (1983) [3H]Bicuculline methochloride binding to low-affinity y-aminobutyric acid receptor sites. J. Neurochem. 41, 1653–1663.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Owen, R. T. and Tyrer, P. (1983) Benzodiazepine dependence. Drugs 25, 385–398.

    PubMed  CAS  Google Scholar 

  • Ozawa, M., Nakada, Y., Sugimachi, K., Yabuuchi, F., Akai, T., Mizuta, E., Kuno, S., and Yamaguchi, M. (1994a) Pharmacological characterisation of the novel nxiolytic ß-carboline in rodents and primates. Jpn. J. Pharmacol. 64, 179–187.

    PubMed  CAS  Google Scholar 

  • Ozawa, M., Sugimachi, K., Nakada-Kometani, Y., Akai, T., and Yamaguchi, M. (1994b) Chronic pharmacological activities of the novel anxiolytic ß-carboline abecarnil in rats. J. Pharmacol. Exp. Ther. 269, 457–462.

    PubMed  CAS  Google Scholar 

  • Panchera, P., Bressa, G. M., and Borghi, C. (1993) Double-blind randomised studies on the therapeutic action of alpidem in generalised anxiety disorders, in Imidazopyridines in Anxiety Disorders: A Novel Experimental and Therapeutic Approach (Bartholini, G., Garreau, M., Morselli, P. L., and Zivkovic, B., eds.), Raven, New York, pp. 155–164.

    Google Scholar 

  • Parola, A. L., Yarnamura, H. I., and Laird, H. E., II (1993) Minireview: peripheral-type benzodiazepine receptors. Life. Sci. 52, 1329–1342.

    Google Scholar 

  • Paul, S. M. and Purdy, R. H. (1992) Neuroactive steroids. FASEB J. 6, 2311–2322.

    PubMed  CAS  Google Scholar 

  • Paysan, J., Bolz, J., Mohler, H., and Fritschy, J. M. (1994) GABAA receptor a, subunit, an early marker for area specification in developing rat cerebral cortex. J. Comp. Neurol. 350, 133–149.

    PubMed  CAS  Google Scholar 

  • Perrault, G., Morel, E., Sanger, D. J., and Zivkovic, B. (1990) Differences in pharmacological profiles of a new generation of benzodiazepine and non-benzodiazepine hypnotics. Eur. J. Pharmacol. 187, 487–494.

    PubMed  CAS  Google Scholar 

  • Perrault, G., Morel, E., Sanger, D. J., and Zivkovic, B. (1992) Lack of tolerance and physical dependence upon repeated treatment with the novel hypnotic zolpidem. J. Pharmacol. Exp. Ther. 263, 290–303.

    Google Scholar 

  • Perrault, G., Morel, E., Sanger, D. J., and Zivkovic, B. (1993) Repeated treatment with alpidem, a new anxiolytic, does not induce tolerance or physical dependence. Neuropharmacology 32, 855–863.

    PubMed  CAS  Google Scholar 

  • Persson, A., Ehrin, E., Eriksson, L., Fardre, L., Hedstrom, C. G., Litton, J. A., Mindus, P., and Sedvall, G. (1985) Imaging of [’’ C]-labelled Ro 15–1788 binding to benzodiazepine receptors in the human brain by positron emission tomography. J. Psychiatr. Res. 19, 609–622.

    Google Scholar 

  • Peters, J. A., Kirkness, E. F., Callachan, H., Lambert, J. J., and Turner, A. J. (1988) Modulation of the GABAA receptor by depressant barbiturates and pregnane steroids. Br. J. Pharmacol. 94, 1257–1269.

    PubMed  CAS  Google Scholar 

  • Petursson, H. and Lader, M. H. (1981) Benzodiazepine dependence. Br. J. Addict. 76, 133–145.

    PubMed  CAS  Google Scholar 

  • Piot, O., Betschart, J., Stutzmann, J. M., and Blanchard, J. C. (1990) Cyclopyrrolones, unlike some benzodiazepines, do not induce physical dependence in mice. Neurosci. Lett. 117, 140–143.

    PubMed  CAS  Google Scholar 

  • Polc, P. (1988) Electrophysiology of benzodiazepine receptor ligands: multiple mechanisms and sites of action. Prog. Neurobiol. 31, 349–424.

    PubMed  CAS  Google Scholar 

  • Potokar, J. and Nutt, D. J. (1994) Anxiolytic potential of benzodiazepine partial agonists. CNS Drugs 1, 305–315.

    Google Scholar 

  • Pribilla, I., Neuhaus, R., Huba, R., Hillmann, M., Turner, J. D., Stephens, D. N., and Schneider, H. H. (1993) Abecarnil is a full agonist at some, and a partial agonist at other recombinant GABAA receptor subtypes. Psychopharmacology Ser. 11, 50–61.

    CAS  Google Scholar 

  • Pritchett, D. B., Lüddens, H., and Seeburg, P. H. (1989a) Type I and type II GABAAbenzodiazepine receptors produced in transfected cells. Science (Wash. DC) 245, 1389–1392.

    Google Scholar 

  • Pritchett, D. B. and Seeburg, P. H. (1990) y-Aminobutyric acidA receptor a5-subunit creates novel type II benzodiazepine receptor pharmacology. J. Neurochem. 54, 1802–1804.

    Google Scholar 

  • Pritchett, D. G., Sontheimer, H., Shivers, B. D., Ymer, S., Kettenmann, H., Schofield, P. R., and Seeburg, P. H. (1989b) Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology. Nature 338, 582–585.

    Google Scholar 

  • Puia, G., Ducic, I., Vicini, S., and Costa, E. (1992) Molecular mechanisms ofthe partial allosteric modulatory effects of bretazenil at y-aminobutyric acid type A receptor. Proc. Natl. Acad. Sci. 89, 3620–3624.

    PubMed  CAS  Google Scholar 

  • Puia, G., Vicini, S., Seeburg, P. H., and Costa, E. (1991) Influence of recombinant yaminobutyric acidA receptor subunit composition on the action of allosteric modulators of y-aminobutyric acid-gated Cl currents. Mol. Pharments. Mol. Pharmacol. 39, 691–696.

    CAS  Google Scholar 

  • Richards, J. G., Schoch, P., and Haefely, W. (1991) Benzodiazepine receptors: new vistas. Semin. Neurosci. 3, 191–203.

    Google Scholar 

  • Rickels, K. and Schweizer, E. E. (1987) Current pharmacotherapy of anxiety and panic, in Psychopharmacology, The Third Generation of Progress ( Meltzer, H.Y., ed.), Raven, New York, pp. 1193–1203.

    Google Scholar 

  • Ruano, D., Benavides, J., Machado, A., and Vitorica, J. (1993) Regional differences in the enhancement by GABA of [3H]zolpidem binding to w, sites in rat brain membranes and sections. Brain Res. 600, 134–140.

    PubMed  CAS  Google Scholar 

  • Samson, Y., Hantraye, P., Baron, J. C., Soussaline, F., and Maziere, M. (1985) Kinetics and displacement of [“C] Ro 15–1788, a benzodiazepine antagonist studied in human brain in vivo by positron tomography. Eur. J. Pharmacol. 110, 247–251.

    PubMed  CAS  Google Scholar 

  • Sanger, D. J., Perrault, G., Morel, E., Joly, D., and Zivkovic, B. (1993) The psychopharmacological profile of alpidem, in Imidazopyridines in Anxiety Disorders: A Novel Experimental and Therapeutic Approach ( Bartholini, G., Garreau, M., Morselli, P. L., and Zivkovic, B., eds.), Raven, New York, pp. 73–84.

    Google Scholar 

  • Sannerud, C. A., Ator, N. A., and Griffiths, R. R. (1992) Behavioural pharmacology of abecarnil in baboons: self-injection, drug discrimination and physical dependence. Behan Pharmacol. 3, 507–516.

    CAS  Google Scholar 

  • Sannerud, C. A., Ator, N. A., and Griffiths, R. R. (1993) Behavioural pharmacology of abecarnil in baboons: reduced dependence and abuse potential. Psychopharmacol. Ser. 11, 113–119.

    PubMed  CAS  Google Scholar 

  • Sapp, D. W., Witte, U., Turner, D. M., Longoni, B., Kokka, N., and Olsen, R. W. (1992) Regional variation in steroid anaesthetic modulation of [35S]TBPS binding to y-aminobutyricp, receptors in rat brain. Am. Soc. Pharm. Exp. Ther. Mol. Pharmacol. 262, 801–808.

    CAS  Google Scholar 

  • Savic, I. Persson, A., Roland, P., Pauli, S. Sedvall, G., and Widen, L. (1988) In vivo demonstration of reduced benzodiazepine receptor binding in human epileptic foci. Lancet 2, 863–866.

    Google Scholar 

  • Schneider, H. H. and Stephens, D. N. (1988) Co-existence of kindling induced by 13-carboline, FG 7142 and tolerance to diazepam following chronic treatment in mice. Eur. J. Pharmacol. 154, 35–45.

    PubMed  CAS  Google Scholar 

  • Schoh, P., Moreau, J. L., Martin, J. R., and Haefely, W. E. (1993) Aspects of benzodiazepine receptor structure and function with relevance to drug tolerance and dependence. Biochem. Soc. Symp. 59, 121–134.

    Google Scholar 

  • Schousboe, A. and Redburn, D. A. (1995) Modulatory actions of y-aminobutyric acid (GABA) on GABA type A receptor subunit expression and function. J. Neurosci. Res. 41, 1–7.

    PubMed  CAS  Google Scholar 

  • Segal, M. and Barker, J. L. (1984) Rat hippocampal neurones in culture: properties of GABA activated Cl-ion conductance. J. Neurophysiol. 55, 500–515.

    Google Scholar 

  • Serra, M., Ghiani, C. A., Motzo, C., and Biggio, G. (1993) Pharmacological evidence for full agonist activity of abecarnil at certain GABAA receptors. Pharmacol. Ser. 11, 62–78.

    CAS  Google Scholar 

  • Serra, M., Ghiani, C. A., Motzo, C., Cuccheddu, T., Floris, S., Giusti, P., and Biggio, G. (1994) Imidazenil, a new partial agonist of benzodiazepine receptors, reverses the inhibitory action of isoniazid and stress on y-aminobutyric acidA receptor function. J. Pharmacol. Exp. Ther. 269, 32–38.

    PubMed  CAS  Google Scholar 

  • Sieghart, W. (1989) Multiplicity of GABAA-benzodiazepine receptors. Trends Pharmacol. Sci. 10, 407–411.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Sieghart, W. and Schlerka, W. (1991) Potency of several type I-benzodiazepine receptor ligands for inhibition of [3H]flunitrazepam binding in different rat brain tissues. Eur. J. Pharmacol. 197, 103–107.

    PubMed  CAS  Google Scholar 

  • Skolnick, P., Crawley, J. N., Glowa, J. R., and Paul, S. M. (1984) 0-Carboline-induced anxiety states. Psychopathology 17, 52–60.

    Google Scholar 

  • Smith, G. B. and Olsen, R. W. (1995) Functional domains of GABAA receptors. Trends Pharmacol. Sci. 16, 162–167

    PubMed  CAS  Google Scholar 

  • Spencer, C. M. and Benfield, P. (1995) Abecarnil in generalised anxiety disorder: an initial appraisal of its clinical potential. CNS Drugs 3, 69–82.

    Google Scholar 

  • Squires, R. F., Benson, D. I., Braestrup, C., Coupet, J., Klepner, C. A., Myers, V., and Beer, B. (1979) Some properties of brain specific benzodiazepine receptors: new evidence for multiple receptors. Pharmacol. Biochem. Behan 10, 825–830.

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Squires, R. F., Casida, J. E., Richardson, M., and Saederup, E. (1983) [35S]-tbutylbicyclophosphorothionate binds with high affinity to brain specific sites coupled to y-aminobutyric acidA and ion recognition sites. Mol. Pharmacol. 23, 326–336.

    Google Scholar 

  • Stephens, D. N., Schneider, H. H., Kehr, W., Andrews, J. S., Rettig, K. J., Turski, L., Schmiechen, R., Turner, J. D., Jensen, L. H., Petersen, E. N., Honore, T., and Hansen, J. B. (1990) Abecarnil, a metabolically stable, anxioselective 3-carboline acting at benzodiazepine receptors. J. Pharmacol. Exp. Ther. 253, 334–343.

    Google Scholar 

  • Stephens, D.N., Turski, L., Hillman, M., Turner, J. D., Schneider, H. H., and Yamaguchi, M. (1992) What are the differences between abecarnil and conventional benzodiazepine anxiolytics? in GABAergic Synaptic Transmission (Biggio, G., Concas, A., and Costa, E., eds.), Raven, New York, pp. 395–405.

    Google Scholar 

  • Stephens, D. N., Turski, L., Jones, G. H., Steppuhn, K. G., and Schneider, H. H. (1993) Abecarnil: a novel anxiolytic with mixed full agonist/partial agonist properties in animal models of anxiety and sedation. Psychopharmacol. Ser. 11, 79–95.

    PubMed  CAS  Google Scholar 

  • Stephenson, F. A., Duggan, M. J. and Pollard, S. (1990) The y2-subunit is an integral component of the y-aminobutyric acidA receptor, but the a, polypeptide is the principal site of the agonist benzodiazepine photoaffinity labeling reaction. J. Biol. Chem. 265 21,160–21,165.

    Google Scholar 

  • Steppuhn, K. G., Schneider, H. H., Turski, L., and Stephens, D. N. (1992) Long-term treatment with abecarnil does not induce diazepam-like dependence in mice. J. Pharmacol. Exp. Ther. 264, 1395–1400.

    Google Scholar 

  • Study, R. E. and Barker, J. L. (1981) Diazepam and (—)pentobarbital: fluctuation analysis reveals different mechanisms for potentiation of y-aminobutyric acid responses in cultured central neurones. Proc. Natl. Acad. Sci. USA 78, 7180–7184.

    Google Scholar 

  • Supavilai, P. and Karobath, M. (1984) [35S]t-butylbicyclophosphorothionate binding sites are constituents of the y-aminobutyric acid benzodiazepine receptor complex. J. Neurosci. 4, 1193–1200.

    Google Scholar 

  • Suzdak, P. D., Glowa, J. R., Crawley, J. N., Schwartz, R. D., Skolnick, P., and Paul, S. M. (1986) A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science (Wash. DC) 234, 1243–1247.

    Google Scholar 

  • Thiebot, M.-H. and Soubrie, P. (1983) Behavioural pharmacology ofthe benzodiazepines, in The Benzodiazepines: From Molecular Biology to Clinical Practice ( Costa, E., ed.), Raven, New York, pp. 67–92.

    Google Scholar 

  • Trifiletti, R. R. and Snyder, S. H. (1984)Anxiolytic cyclopyrrolones zopiclone and suriclone bind to a novel site linked allosterically to benzodiazepine receptors. Mol. Pharmacol. 26, 458–469.

    Google Scholar 

  • Turski, L., Stephens, D.N., Jensen, L.H., Petersen, E. N., Meldrum, B. S., Patel, S., Bondo Hansen, J., Löscher, W., Schneider, H. H., and Schmiechen, R. (1990) Anticonvulsant action of the ß-carboline abecarnil: studies in rodents and baboon, Papio papio. J. Pharmacol. Exp. Ther. 253, 344–352.

    CAS  Google Scholar 

  • Uusi-Oukari, M., and Korpi, E. R. (1990) Diazepam sensitivity of the binding of an imidazobenzodiazepine, [3H]Ro 15–4513, in cerebellar membranes from two rat lines developed for high and low alcohol sensitivity. J. Neurochem. 54, 1980–1987.

    PubMed  CAS  Google Scholar 

  • Wafford, K. A., Bain, C. J., Quirk, K., McKernan, R. M., Wingrove, P. B., Whiting, P. J., and Kemp, J. A. (1994) A novel allosteric modulatory site on the GABAA receptor ß subunit. Neuron 12, 775–782.

    Google Scholar 

  • Wafford, K. A., Burnett, D. M., Leidenheimer, N. J., Burt, D. R., Wang, J. B., Kofuji, P., Dunwiddie, T. V., Harris, R. A., and Sikola, J. M. (1991) Ethanol sensitivity of the GABAA receptor expressed in Xenopus oocytes requires 8 amino acids contained in the y2L-subunit. Neuron 7, 27–33.

    Google Scholar 

  • Wafford, K. A., Whiting, P. J., and Kemp, J. A. (1993) Differences in affinity of benzodiazepine receptor ligands at recombinant y-aminobutyric acidA receptor subtypes. Mol. Pharmacol. 43, 240–244.

    PubMed  CAS  Google Scholar 

  • Whiting, P., McKernan, R. M., and Iversen, L. L. (1990) Another mechanism for creating diversity in y-aminobutyrate type A receptors: RNA splicing directs expression of two forms of y2 subunit one of which contains a protein kinase C phosphorylation site. Proc. Natl. Acad. Sci. USA 87, 9966–9970.

    PubMed  CAS  Google Scholar 

  • Wisden, W., Laurie, D. J., Monyer, H., and Seeburg, P. H. (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J. Neurosci. 12, 1040–1062.

    PubMed  CAS  Google Scholar 

  • Woods, J. H., Katz, J. L., and Winger, G. (1987) Abuse liability of benzodiazepines. Pharmacol. Rev. 39, 251–392.

    Google Scholar 

  • Woods, J. H., Katz, J. L., and Winger, G. (1992) Benzodiazepines: use, abuse and consequences. Pharmacol. Rev. 44, 151–347.

    Google Scholar 

  • Wu, Y., Rosenberg, H. C., and Chiu, T. H. (1995) Rapid down-regulation of [3H]zolpidem binding to rat brain benzodiazepine receptors during flurazepam treatment. Eur. J. Pharmacol. 278, 125–132.

    Google Scholar 

  • Yanganita, T. (1993) Dependence potential of zopiclone studied in monkeys. Pharmacology 27 (Suppl. 2), 216–227.

    Google Scholar 

  • Zhang, P., Lin., U., McKernan, R., Wafford, K., and Cook, J. M. (1995) Studies of novel imidazobenzodiazepine ligands at GABAA/BzR subtypes: effect of C(3) substituents on receptor subtype selectivity. Med. Chem. Res. 5, 487–495.

    CAS  Google Scholar 

  • Zivkovic, B., Morel, E., Joly, D., Perrault, G., Sanger, D. J., and Lloyd, K. G. (1990) Pharmacological and behavioural profile of alpidem as an anxiolytic. Pharmacopsychiatry 23, 108–113.

    PubMed  Google Scholar 

  • Zundel, J. L., Blanchard, J. C., and Julou, L. (1985) Partial chemical characterisation of cyclopyrrolones ([3H]-suriclone) and benzodiazepines ([3H]-flunitrazepam) binding sites differences. Life Sci. 36, 2247–2255.

    PubMed  CAS  Google Scholar 

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  1. Neil Upton
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  2. Thomas Blackburn
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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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Upton, N., Blackburn, T. (1997). Pharmacology of Mammalian GABAA Receptors. 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_4

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