Tricyclic antidepressants block histamine H₁ receptors of mouse neuroblastoma cells [26]

TRICYCLIC antidepressants are structurally related to anti-histamines and are known to possess antihistaminic properties¹. Green and co-workers^2,24 showed that these drugs competitively antagonised histamine H₂ receptor-mediated cyclic AMP formation by homogenates of guinea pig brain. Using muscarinic acetylcholine receptor-mediated cyclic GMP formation by mouse neuroblastoma cells (clone N1E-115)³, the interactions of psychotherapeutic drugs with this cholinergic receptor were studied in this laboratory^4,5. While investigating the desensitisation of this muscarinic receptor⁶, it was found that histamine also stimulated cyclic GMP formation by activation of histamine H ₁ receptors of these cells⁷. This assay for histamine H₁ receptors was used to obtain quantitative data for tricyclic antidepressant interactions with these receptors. This report shows that these drugs are potent competitive inhibitors of histamine H₁ receptors and that some of these compounds are amongst the most potent H₁ antagonists known.