Effects of tetrazole derivatives on [3H]diazepam binding in vitro: correlation with convulsant potency.
A series of 8 tetrazole derivatives which differ more than one hundred-fold in their potencies as convulsants were tested for their abilities to inhibit [3H]diazepam binding to benzodiazepine receptors in vitro. The concentrations of drug necessary to inhibit 50% of specifically bound [3H]diazepam ranges from 18 micro M for undecamethylenetetrazole to 20 mM for trimethylenetetrazole. A comparison of the minimum convulsive doses for the 8 tetrazole derivatives tested with their relative potencies in displacing [3H]diazepam binding in vitro revealed a highly significant correlation (r = 0.98, P less than 0.001). In contrast, several representative tetrazole derivatives were found to have no inhibitory effects on beta-adrenergic, alpha-adrenergic or muscarinic cholinergic receptors in the same membrane preparation. These results suggest that pentamethylenetetrazole and related tetrazole derivatives may elicit their convulsant effects by interaction with the benzodiazepine receptor.
D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D003292:Convulsants; D003975:Diazepam / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000378:metabolism; D011963:Receptors, GABA-A; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000378:metabolism / Q000494:pharmacology*
D001393:Azoles; D003292:Convulsants; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D013777:Tetrazoles; D003975:Diazepam