title: Specificity within the GABAA receptor supramolecular complex: a consideration of the new omega 1-receptor selective imidazopyridine hypnotic zolpidem.
abstract: The relative contribution of different recognition sites within the GABAA receptor supramolecular complex (GRSC) to the pharmacological effects of anxiolytic and hypnotic drugs is unknown. The development of the omega 1 (ex BZ1) specific hypnotic zolpidem allows a more direct approach to the problem. In contrast to many benzodiazepine hypnotic/anxiolytics (e.g., flunitrazepam, diazepam), zolpidem shows a specificity for GABAergic function, e.g., selectively reversing isoniazide-induced seizures. Furthermore, zolpidem produces a highly specific hypnotic action as compared to myorelaxant or amnesic effects (ratio of ED50's greater than 4.0 for zolpidem; less than 1 for flunitrazepam). Zolpidem exerts its action within the GRSC as it enhances 35S-TBPS binding, as do mixed omega 1/omega 2 compounds or GABA agonists. Both the in vivo and in vitro actions of zolpidem are reversed by flumazenil and the enhanced 35S-TBPS binding is also bicuculline-sensitive. Thus, omega 1 recognition site stimulation (e.g., by zolpidem) is sufficient to produce potent pharmacological effects and modulation of the GABAA receptor-gated chloride ionophore.
authors.affiliation: Laboratoires d'Etudes et de Recherche's Synthélabo (L.E.R.S.), Bagneux, France.
authors.forename: K G
authors.initials: KG
authors.lastname: Lloyd
authors.forename: B
authors.initials: B
authors.lastname: Zivkovic
mesh_terms: D000818:Animals; D003975:Diazepam / Q000494:pharmacology; D005445:Flunitrazepam / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011725:Pyridines / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000032:analysis* / Q000145:classification; D000077334:Zolpidem
chemical_list: D006993:Hypnotics and Sedatives; D011725:Pyridines; D011963:Receptors, GABA-A; D005445:Flunitrazepam; D000077334:Zolpidem; D003975:Diazepam