TY - JOUR
T1 - Effects of tetrazole derivatives on [3H]diazepam binding in vitro
T2 - Correlation with convulsant potency
AU - Rehavi, Moshe
AU - Skolnick, Phil
AU - Paul, Steven M.
PY - 1982/3/12
Y1 - 1982/3/12
N2 - 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.
AB - 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.
KW - Benzodiazepine receptors
KW - Convulsants
KW - Pentamethylenetetrazole
KW - Tetrazole derivatives
UR - http://www.scopus.com/inward/record.url?scp=0020045631&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(82)90037-1
DO - 10.1016/0014-2999(82)90037-1
M3 - Article
C2 - 6279412
AN - SCOPUS:0020045631
SN - 0014-2999
VL - 78
SP - 353
EP - 356
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 3
ER -