Effects of clonidine and tricyclic antidepressants on gastric smooth muscle contractility

Abstract

To determine if and how clonidine and tricyclic antidepressants affect gastric contractility. Guinea pig fundic and antral circular muscle strips were studied in vitro. The effects of clonidine or amitriptyline added in graded concentrations on contractions to electric field stimulation (EFS), acetylcholine (ACh), and SP in the presence of N(epsilon)-nitro-l-arginine methyl ester (l-NAME) were studied. EFS produced frequency dependent contractions of fundic and antral muscle that were abolished by atropine or tetrodotoxin (TTX). ACh contractions were abolished by atropine but not TTX. Clonidine reduced contractile response to EFS but had no effect on ACh contractions. The threshold concentration of clonidine to inhibit EFS contractions was lower in the fundus than in the antrum. Amitriptyline reduced contractions to both EFS and ACh but not to SP. The threshold concentration of amitriptyline to inhibit EFS contractions was lower in the antrum than in the fundus. Both clonidine and amitriptyline affect gastric contractility. At threshold concentrations, clonidine affects fundic contractility whereas amitriptyline affects antral contractility. Clonidine affects gastric contractility in response to EFS but not to ACh, suggesting alpha-2 receptors on cholinergic nerves that reduce ACh release. Amitriptyline inhibits gastric contractility to EFS and ACh suggesting an inhibitory muscle effect.

Wistar Kyoto rats have impaired gastric accommodation compared to Sprague Dawley rats due to increased gastric vagal cholinergic tone

“…The role of sympathetic neuronal input in modulating gastric vagal cholinergic functions has been well studied and several investigators have reported that alpha-2 adrenoceptors are present presynaptically on cholinergic nerves [36]. Studies in fundus preparations from various species have shown that stimulation of alpha-2 adrenoceptors inhibits both the release of ACh and the neuronal-induced contractions [37,38]. Therefore, it is reasonable to believe that the effect of clonidine in WKY rats is at least partly mediated through stimulation of alpha-2 adrenoceptors located presynaptically on cholinergic myenteric neurons, resulting in reduced ACh release that normalizes the disturbed vagal cholinergic transmission.…”

Effects of amitriptyline, a tricyclic antidepressant, on smooth muscle reactivity in isolated rat trachea

“…James et al [16] observed that effects of tricyclic antidepressants on gastric smooth muscle contractility in guinea pig, and found that amitriptyline reduced contractions induced by ACh. Huang & Lau [17] reported that in the rat isolated trachea, amitriptyline produced a shift to the right of ACh concentration-contraction curve without affecting the maximum contraction.…”

Empirically Supported Use of Psychiatric Medications in Adolescents and Adults with IBD

“…Largely mediated by anticholinergic activity, most studies with TCAs show a delayed transit 86,[159][160][161] or decreased muscle activity. 162,163 Reported effects on pain levels prompted investigations on visceral sensation with variable findings. Using balloon distension as a physiologically relevant stimulus, most studies found no or at best marginal effects on responses to esophageal, 164,165 gastric, 162 or rectal distension 166 in humans.…”