Stereoisomeric tetrahydro-beta-carbolines differ in their interaction with rat brain benzodiazepine receptors.
A series of (+) and (-) tetrahydro-beta-carboline-3-carboxamide stereoisomers related to the ethyl ester of beta-carboline-3-carboxylate (beta-CCE) have been tested for their ability to displace 3H-flunitrazepam from binding sites prepared from rat cerebral cortex (benzodiazepine receptors). The (+) stereoisomers of ethyl and propyl 1,2,3,4-tetrahydro-beta-carboline-3-carboxamides were the most potent inhibitors of specific 3H-flunitrazepam binding and had significantly lower IC50s than the corresponding (-) isomers. Although the IC50 values for this series of tetrahydro-beta-carboline-3-carboxamides were about 1000 fold higher than the IC50 value for beta-CCE, these compounds were as potent as the beta-carboline alkaloids harmane and harmine. The title compounds may be useful stereoisomeric probes for the characterization of subtypes of specific benzodiazepine binding sites.
D000818:Animals; D001667:Binding, Competitive; D002243:Carbolines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D007211:Indoles / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A; D013237:Stereoisomerism
D002243:Carbolines; D007211:Indoles; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005445:Flunitrazepam; C009804:tryptoline