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Anticholinergic activity of imipramine and some analogs at muscarinic receptors of cultured mouse neuroblastoma cells

Abstract

Imipramine and some of its analogs (trimipramine, 3-chlorimipramine, desipramine, 3-chloro-2-hydroxyimipramine, 2-hydroxyimipramine, and didesmethylimipramine), were assayed for their potencies as antimuscarinic agents by their abilities to antagonize muscarinic receptor-mediated cyclic guanosine monophosphate (GMP) formation by cultured mouse neuroblastoma cells. Equilibrium dissociation constants for these compounds yielded the following rank order of potency at the muscarinic receptor: imipramine > trimipramine > 3-chlorimipramine > desipramine > 3-chloro-2-hydroxyimipramine > 2-hydroxyimipramine > didesmethylimipramine. These results indicate that didesmethylation of the side chain nitrogen or hydroxylation of the ring at the 2-position lead to marked reductions (30-fold and 12-fold, respectively) in antimuscarinic activity of imipramine.

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Correspondence to Elliott Richelson.

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Petersen, R.C., Richelson, E. Anticholinergic activity of imipramine and some analogs at muscarinic receptors of cultured mouse neuroblastoma cells. Psychopharmacology 76, 26–28 (1982). https://doi.org/10.1007/BF00430749

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Key words

  • Tricyclic antidepressants
  • Antimuscarinic activity