Interaction of histamine H2-receptor antagonists with GABA and benzodiazepine binding sites in the CNS.

The histamine H2-receptor antagonist cimetidine potently inhibited [3H]muscimol and enhanced [3H]flunitrazepam binding in membranes prepared from several brain regions in the rat, including the dorsal raphe nucleus. As further examined in cortical membranes, this effect on both GABA and benzodiazepine binding sites was specific for imidazole-derived H2-receptor antagonists (potency: cimetidine greater than metiamide greater than tiotidine) and not observed with either several H1-receptor antagonists or histamine. These data indicate a striking similarity between the actions of cimetidine (and other imidazole-derived H2-receptor antagonists) and GABA on binding parameters at the GABA receptor complex.