Interaction of stereoisomers of barbiturates with [3H]alpha-dihydropicrotoxinin binding sites.
Racemic depressant barbiturates inhibit the binding of gamma-aminobutyric acid antagonist [3H]alpha-dihydropicrotoxinin (DHP) to rat brain membranes with IC50 values ranging from 5 to 50 microM. The (-) isomers of pentobarbital and secobarbital were three to four-fold more potent that their (+) isomers in inhibiting [3H]DHP binding. In contrast, the (+) isomer of hexobarbital was a better inhibitor than (-) hexobarbital. The stereoisomers of 1-methyl-5-phenyl-5-propylbarbituric acid (MPPB), which show opposite pharmacological activity, inhibited [3H]DHP binding in a biphasic manner with a plateau at 4-100 nM MPPB. These results suggest heterogeneity of DHP binding sites. The possibility that depressant and convulsant barbiturates may act at the level of DHP site at the GABA synapse is discussed.
D000818:Animals; D001463:Barbiturates / Q000494:pharmacology; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010852:Picrotoxin / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001463:Barbiturates; D010852:Picrotoxin; D011955:Receptors, Drug; D011963:Receptors, GABA-A; C031012:dihydropicrotoxinin receptor; C017230:dihydropicrotoxinin