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 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.
D000818:Animals; D002999:Clone Cells; D006152:Cyclic GMP / Q000378:metabolism; D007099:Imipramine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013329:Structure-Activity Relationship
D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D006152:Cyclic GMP; D007099:Imipramine