The effect of amitriptyline, mianserin, and viloxazine at pre- and post-junctional muscarinic receptors in guinea-pig ileal longitudinal muscle.
The antimuscarinic activity of amitriptyline, mianserin, and viloxazine was compared with atropine in guinea-pig ileal longitudinal muscle. The pA2 values obtained using carbachol (CCh) as agonist were as follows: atropine, 9.55; amitriptyline, 7.50; mianserin, 6.40; and viloxazine, 4.91. Responses to transmural electrical stimulation (1-50 Hz) were more resistant than those produced by CCh to inhibition by atropine and the antidepressants. This did not appear to be due to a selective inhibition of prejunctional inhibitory muscarinic receptors, as a pA2 of 8.73 was obtained with atropine for the depression of oxotremorine-induced inhibition of acetylcholine (ACh) output. Amitriptyline (10 micrometers) caused a 2.4-fold increase in ACh output and was 200-fold weaker than atropine at doubling ACh output in the longitudinal muscle stimulated at 0.3 Hz. Mianserin (10 micrometers) and viloxazine (1-10 micrometers) did not significantly affect ACh output. It is suggested that the antidepressants exhibits a greater affinity for the postjunctional muscarinic receptors in the guinea-pig ileal longitudinal muscle.
D000109:Acetylcholine / Q000494:pharmacology; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects*; D010095:Oxotremorine / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014745:Viloxazine / Q000494:pharmacology
D000928:Antidepressive Agents; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D000639:Amitriptyline; D008803:Mianserin; D014745:Viloxazine; D010095:Oxotremorine; D001285:Atropine; D002217:Carbachol; D000109:Acetylcholine