Acute and chronic effects of desvenlafaxine on gastrointestinal transit and motility in dogs

Background: Antidepressants are commonly used for treating functional gastrointestinal (GI) diseases. However, little is known whether antidepressants improve or impair GI motility. This study aimed at exploring possible effects of a serotonin-norepinephrine reuptake inhibitor, desvenlafaxine succinate (DVS), on GI motility in dogs. Methods: Eight dogs chronically implanted with a duodenal cannula and a colon cannula were used in the study. Experiments were performed to assess the effects of a single dose of DVS (50 or 100 mg) and DVS given 50 mg once a day for 2 weeks on gastric emptying of solid, small intestinal transit, and colon transit and contractions. Key Results: (1) DVS significantly delayed gastric emptying of solid at a single dose of 50 or 100 mg. The inhibitory effect on gastric emptying was completely blocked by guanethidine (an adrenergic blocking agent). (2) DVS at a single dose of 50 or 100 mg accelerated colon transit, but showed no effects on small bowel transit. (3) DVS at a single dose of 50 mg enhanced colon contractions and guanethidine blocked the effect. (4) Surprisingly, DVS given at 50 mg once daily for 2 weeks did not alter gastric emptying, small bowel transit or colon transit. Conclusions & Inferences: Acute DVS delays gastric emptying of solid and enhances the contractions of the colon, which may be mediated via the sympathetic mechanism. Acute DVS promotes the transit of the colon but not the small intestine. However, chronic administration of DVS does not seem to alter GI motility.