Structure-activity studies on the potentiation of benzodiazepine receptor binding by ethylenediamine analogues and derivatives.
The effect of ethylenediamine analogues on in vitro binding of [3H]-diazepam to crude cerebral cortical synaptosomal membranes in the rat was studied. Ethylenediamine significantly increased [3H]-diazepam binding to a maximum potentiation of 154% control (EC50 = 1.8 X 10(-4) M) and was the most active compound studied in terms of both potency and the maximum potentiation observed. Potentiation of [3H]-diazepam binding by ethylenediamine analogues is dependent on carbon-chain length, appears to require two terminal amino groups, and is not observed in the rigid analogues studied. Potentiation of [3H]-diazepam binding by ethylenediamine analogues is mediated largely by a change in receptor number and not receptor affinity. Results are discussed in terms of the possible nature of the ethylenediamine binding site.
D000818:Animals; D001921:Brain / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D004357:Drug Synergism; D005029:Ethylenediamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A; D013329:Structure-Activity Relationship
D005029:Ethylenediamines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D003975:Diazepam