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

✍ Scribed by Ronald C. Petersen; Elliott Richelson

• Book ID: 104770969
• Publisher: Springer
• Year: 1982
• Tongue: English
• Weight: 263 KB
• Volume: 76
• Category: Article
• ISSN: 0033-3158
• DOI: 10.1007/bf00430749

✦ Synopsis

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 greater than trimipramine greater than 3-chlorimipramine greater than desipramine greater than 3-chloro-2-hydroxyimipramine greater than 2-hydroxyimipramine greater than 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.