Molecular Heterogeneity of GABAA-Benzodiazepine Receptors

  • W. Sieghart
  • K. Fuchs
Conference paper
Part of the NATO ASI Series book series (volume 32)


Since the introduction of benzodiazepines into clinical use and the establishment of their therapeutic action as anxiolytics, anticonvulsants, muscle relaxants and sedative hypnotics (Randall, 1961) a wealth of information has been accumulated on the molecular mechanism of action of these compounds. Thus, electrophysiological investigations have indicated that benzodiazepines exert most of their actions by enhancing the postsynaptic effects of the putative neurotransmitter GABA (Haefely et al., 1981). Biochemical and pharmacological investigations have established the existence of a high affinity binding site for benzodiazepines in brain membranes (Braestrup and Squires, 1977; Möhler and Okada, 1977) and demonstrated an excellent correlation between the clinical potency of a series of benzodiazepines and their ability to displace 3H-diazepam or 3H-flunitrazepam from their high affinity binding sites. Thus, it was concluded that these sites are the physiological receptors by which benzodiazepines exert their pharmacologically and clinically relevant actions.


High Affinity Binding Site Sedative Hypnotic Clinical Potency Diazepine Receptor Bovine Cerebral Cortex 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arbilla S, Depoortere H, George P, Langer SZ (1985) Pharmacological profile of the Imidazopyridine Zolpidem at benzodiazepine receptors and electrocorticogram in rats. Naunyn-Schmiedeberg1s Arch Pharmacol 330: 248–251CrossRefGoogle Scholar
  2. Barnard EA, Stephenson FA, Sigel E, Mamalaki C, Bilbe G, Constanti A, Smart TE, Brown DA (1984) Structure and properties of the brain GABA/benzodiazepine receptor complex. In: Kito S, Segawa T, Kuriyama K, Yamamura HI, Olsen RW (eds) Neurotransmitter receptors: mechanisms of action and regulation. Plenum Press, New York, p 235Google Scholar
  3. Bowling AC, De Lorenzo RJ (1982) Micromolar affinity benzodiazepine receptors identification and characterization in central nervous system. Science 216: 1247–1250PubMedCrossRefGoogle Scholar
  4. Braestrup C, Squires R (1977) Specific benzodiazepine receptors in rat brain characterized by high affinity 3H-diazepam binding. Proc Natl Acad Sei USA 74: 3804–3809CrossRefGoogle Scholar
  5. Braestrup C, Nielsen MJ (1983) Benzodiazepine receptors. In: Iversen L, Iversen SD, Snyder, SH (eds) Handbook of psycho-pharmacology, vol. 17. Plenum Publishing Corp., p 285Google Scholar
  6. Fuchs K, Möhler H, Sieghart W (1988) Various proteins from rat brain, specifically and irreversibly labeled by 3H-flunittrazepam are distinct α-subunits of the GABA-benzodiazepine receptor complex. Neurosci Letters 90: 314–319CrossRefGoogle Scholar
  7. Haefely W, Pieri L, Pole P, Schaffner R (1981) General pharmacology and neuropharmacology of benzodiazepine derivatives. In: Hoffmeister E, Stille G (eds) Handbook of Experimental Pharmacology, Vol.55/11, Springer Verlag, Berlin, p 134Google Scholar
  8. Häring P, Stähli C, Schoch P, Takacs B, Staehelin T, Möhler H (1985) Monoclonal antibodies reveal structural homogeneity of γ-aminobutyric acid/benzodiazepine receptors in different brain areas. Proc Natl Acad Sci USA 82: 4837–4841PubMedCrossRefGoogle Scholar
  9. Klepner CA, Lippa AS, Benson DI, Sano MC, Beer B (1979) Resolution of two biochemically and pharmacologically distinct benzodiazepine receptors. Pharmacol Biochem Behav 11: 457–462PubMedCrossRefGoogle Scholar
  10. Lippa AS, Jackson D, Wennogle LP, Beer B, Meyerson LR (1982) Non benzodiazepine agonists for benzodiazepine receptors. In: Usdin E, Skolnick Ph, Tallman JF, Greenblatt D, Paul SM (eds) Pharmacology of Benzodiazepines, Macmillan Press Ltd., London and Basingstoke, p 431Google Scholar
  11. Möhler H, Okada T (1977) Benzodiazepine receptors — demonstration in the central nervous system. Science 198: 849–851PubMedCrossRefGoogle Scholar
  12. Olsen RW (1982) Drug interactions at the GABA receptor ionophore complex. Ann Rev Pharmacol Toxicol 22: 245–277CrossRefGoogle Scholar
  13. Randall LO (1961) Pharmacology of chlordiazepoxide (Librium). Dis Nerv System 22, Sect 2, Suppl 7: 7–15Google Scholar
  14. Schoch P, Richards JG, Häring P, Takacs B, Stähli C, Staehelin T, Haefely W, Möhler H (1985) Co-localization of GABAA receptors and benzodiazepine receptors in the brain shown by monoclonal antibodies. Nature 314: 168–171PubMedCrossRefGoogle Scholar
  15. Schoemaker H, Bliss, M, Yamamura HI (1981) Specific high affinity binding of 3H-Ro 5–4864 to benzodiazepine binding sites in rat cerebral cortex. Europ J Pharmacol 71:173–175Google Scholar
  16. Sieghart W, Karobath M, (1980) Molecular heterogeneity of benzodiazepine receptors. Nature 286: 285–287PubMedCrossRefGoogle Scholar
  17. Sieghart W, Mayer A, Drexler G (1983) Properties of 3H-flunitrazepam binding to different benzodiazepine binding proteins. Europ J Pharmacol 88: 291–299CrossRefGoogle Scholar
  18. Sieghart W, Schuster A (1984) Affinity of various ligands for benzodiazepine receptors in rat cerebellum and hippocampus. Biochem Pharm 33: 4033–4038PubMedCrossRefGoogle Scholar
  19. Sieghart W, Eichinger A, Zezula J (1987) Comparison of tryptic peptides of benzodiazepine binding proteins photolabeled with 3H-flunitrazepam or 3H-Ro 15–4513. J Neurochem 48: 1109–1114PubMedCrossRefGoogle Scholar
  20. Sieghart W (1988) Comparison of two different benzodiazepine binding proteins by peptide mapping after limited proteolysis. Brain Res 450: 387–391PubMedCrossRefGoogle Scholar
  21. Sigel E, Stephenson FA, Mamalaki C, Barnard E (1983) γ-aminobutyric acid/benzodiazepine receptor complex of bovine cerebral cortex. Purification and partial characterization. J Biol Chem. 258: 6965–6971PubMedGoogle Scholar
  22. Stapleton SR, Prestwich SA, Horton RW (1982) Regional heterogeneity of benzodiazepine binding sites in rat brain. Europ J Pharmacol 84: 221CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • W. Sieghart
    • 1
  • K. Fuchs
    • 1
  1. 1.Department of Biochemical PsychiatryPsychiatrische UniversitätsklinikViennaAustria

Personalised recommendations