Antidepressants are weak competitive antagonists of histamine H₂ receptors in dissociated brain tissue

Guinea pig hippocampus dissociated by mechanical means into uniform clumps of cells (∼ 100 μm in diameter) contains histamine receptors (H₁ and H₂) which mediate the formation of cyclic AMP. In this preparation, antidepressants are very potent antagonists of histamine H₁ receptors but are weak antagonists of histamine H₂ receptors. The latter result is contrary to data derived by others using homogenates of the guinea pig hippocampus and seems to dispel the idea that antidepressants derive their efficacy by blocking histamine H₂ receptors in brain.