High affinity [3H]zolpidem binding in the rat brain: an imidazopyridine with agonist properties at central benzodiazepine receptors.
[3H]Zolpidem, a novel hypnotic drug possessing a chemical structure unrelated to that of benzodiazepine (BZD) was employed as a new ligand to determine its binding characteristics to membrane preparations of rat cerebral cortex and cerebellum. In both structures, the imidazopyridine [3H]zolpidem bound with high affinity to a single population of recognition sites. The cerebellum possessed a similar number of [3H]zolpidem and [3H]diazepam binding sites, while the cerebral cortex possessed a lower density of [3H]zolpidem than [3H]diazepam binding sites. In contrast to [3H]diazepam binding, [3H]zolpidem binding was not detectable in the spinal cord. In the cortex, BZDs had a similar potency to displace [3H]zolpidem and [3H]diazepam binding while non-BZDs were more potent to inhibit [3H] zolpidem binding than [3H]diazepam binding. The binding of [3H]zolpidem was enhanced by GABA to the same extent as [3H]diazepam binding. The increase in [3H] zolpidem binding caused by chloride ions was less pronounced than that in [3H]diazepam binding. It is concluded that [3H]zolpidem possesses selectivity for BZD receptors with the pharmacological characteristics and regional distribution of the BZD1 receptor subtype. [3H]Zolpidem as a radioligand offers a useful additional tool to study the mechanism of action of hypnotics acting through BZD receptor subtypes.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001569:Benzodiazepines; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011725:Pyridines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D000077334:Zolpidem
D014151:Anti-Anxiety Agents; D011725:Pyridines; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000077334:Zolpidem