Enhancement of 3H-phenytoin binding by diazepam and (+)bicuculline.
3H-Phenytoin binding to the particulate fraction of rat wholebrain homogenate was studied using the filter assay technique. It was found that diazepam and (+)bicuculline methobromide caused a concentration-dependent enhancement of the total binding of 3H-phenytoin, whereas GABA and (-)bicuculline methobromide (the inactive bicuculline isomer) had no effect. In subsequent competition experiments (labelled versus unlabelled phenytoin), it was found that the presence of a potentiating concentration of diazepam transformed the biphasic phenytoin competition isotherm into a simple curve with a Hill coefficient of approximately one, and a Ki of 110 nM.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010672:Phenytoin / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D003975:Diazepam; D001640:Bicuculline