Properties of phenytoin binding sites in the rat brain: regional distribution and postnatal development

Specific [3H]phenytoin binding in rat cortical membranes is associated with a micromolar affinity site through which diazepam can exert an enhancing effect. In contrast to diazepam, (+)bicuculline, isoguvacine and pentobarbital inhibited phenytoin binding, while GABA and (-)baclofen had no effect. Decreased phenytoin binding and a loss of the diazepam effect were observed in phospholipase A2-treated membranes. Binding in the absence and presence of diazepam demonstrated differential postnatal development. Furthermore, the degree to which binding was enhanced by diazepam varied from one brain region to another. The regional variations of phenytoin binding, both in the presence and absence of diazepam, did not correlate positively with the regional distribution of either the central benzodiazepine receptors or the peripheral type binding sites in the brain.