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 μM 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<0.001). In contrast, several representative tetrazole derivatives were found to have no inhibitory effects on β-adrenergic, α-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.
