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


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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  1. Cheng YC, Prusoff WH (1973) Relationship between the inhibition constant (Ki) and the concentration of inhibitor which caused 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3095–3108

  2. Kessler KA (1978) Tricyclic antidepressants: Mode of action had clinical use. In: Lipton MA, DiMascio A, Killam KF (eds) Psychopharmacology: A generation of progress. Raven, New York, p 1289

  3. Potter WZ, Calil HM, Manian AA (1979) Hydroxylated metabolites of tricyclic antidepressants: Preclinical assessment of activity. Biol Psychol 14:601–613

  4. Potter WZ, Calil HM, Zavadil AP, Sutfin T, Jusko WJ, Rapaport, J, Goodwin FK (1980) Steady state concentration of hydroxylated metabolites of tricyclic antidepressants in patients: Relationship to clinical effect. Psychopharmacol Bull 16:32–34

  5. Richelson E (1978) Tricyclic antidepressants block histamine H1 receptors of mouse neuroblastoma cells. Nature 274:176–177

  6. Richelson E (1979a) Tricyclic antidepressants and neurotransmitter receptors. Psychiatric Annals 9:4–13

  7. Richelson E (1979b) Tricyclic antidepressants and histamine H1 receptors. Mayo Clin Proc 54:669–674

  8. Richelson E, Prendergast FG, Divinetz-Romero S (1978) Muscarinic receptor-mediated cyclic GMP formation by cultured nerve cells: Ionic dependence and effects of local anesthetics. Biochem Pharmacol 27:2039–2048

  9. Shein K, Smith SE (1978) Structure-activity relationships for the anticholinoceptor action of tricyclic antidepressants. Br J Pharmacol 62:567–571

  10. Waud D (1976) Analysis of dose-response relationship. Adv Gen Cell Pharmacol 1:145–178

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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