The benzodiazepine receptor and sleep.
The discovery of high affinity, stereoselective binding sites for benzodiazepines (BZ) was a major step in understanding the molecular mechanism by which these widely used sedative/hypnotics exert their various pharmacologic effects. It has become clear that the BZ receptor complex has functional significance in terms of the anxiolytic, anticonvulsant and muscle relaxant properties of these widely used compounds. Until recently its role in the sleep-inducing properties has been unclear. This paper reviews a series of studies indicating that the BZ receptor complex does indeed mediate the hypnotic effects of flurazepam, and that these effects may involve alterations in calcium flow across neuronal membranes. Preliminary evidence also suggests that some pharmacologic properties of barbiturates may involve interactions with portions of the benzodiazepine receptor complex. Lethality from pentobarbital in mice, for instance, can be greatly reduced by treatment with IPPO, a compound which binds in relation to the chloride ionophore. The implications of sub-types of BZ receptors are discussed. Experience with some compounds which bind at the BZ receptor suggests that in the future drugs may become available which are much more specific for individual desired effects.
D000818:Animals; D001463:Barbiturates / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002243:Carbolines / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D005442:Flumazenil; D005479:Flurazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D009043:Motor Activity / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology / Q000633:toxicity; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects*; D013574:Synaptosomes / Q000378:metabolism
D001463:Barbiturates; D001570:Benzodiazepinones; D002243:Carbolines; D011720:Pyrazoles; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil; C031516:3-hydroxymethyl-beta-carboline; C024915:beta-carboline-3-carboxylic acid ethyl ester; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D009543:Nifedipine; D005479:Flurazepam; D003975:Diazepam; D002118:Calcium; D010634:Phenobarbital