Brain histamine H1- and H2-receptors and histamine-sensitive adenylate cyclase: effects of antipsychotics and antidepressants.

Several classes of psychoactive compounds have been investigated for their effects on histamine-sensitive adenylate cyclase in cell free preparations from the guinea-pig cerebral cortex. Their inhibitory actions on this enzyme system have been compared with their abilities to displace [3H]pyrilamine and [3H]cimetidine from histamine H1- and H2-receptor sites, respectively. The results of these studies show that compounds which inhibited the histamine-sensitive cyclase were also displacers of either ([3H]pyrilamine or [3H]cimetidine or both 3H]ligands from their binding sites. In spite of the lack of a correlation between binding and cyclase antagonism, it was observed that compounds that displace both ligands showed greater inhibition of the cyclase than those that have affinities for sites labeled by one or the other ligand. It was concluded that antihistamines, the antipsychotics and the antidepressants share a common property through their antagonism of H1-receptors and that may be responsible for their sedative side effect.