Excitatory Effects of Mirtazapine on Gastric and Colonic Motility

Purpose: Mirtazapine (Mirt.) is an antidepressant commonly used in the clinical practice for irritable bowel syndrome. Our previous studies reported that mirt. reduced visceral hypersensitivity in rodent model of colonic sensitization. However, the effect of mirt. on gastrointestinal motility is unknown. The aims of this study were to investigate the effects of mirt. on gastrointestinal motility including solid gastric emptying, antral contractions, small intestinal contractions, small intestinal transit and colonic transit in dogs. Methods: Eleven dogs were used in this study, 6 of the dogs were chronically implanted with two cannulas, one was located at the duodenum and the other at the ascending colon; 5 of the dogs were implanted with one gastric cannula for measuring antral contractions. Each of the motility tests was performed in 2 randomized sessions (control, mirtazapine 45 mg/kg). Two additional sessions were included for the gastric emptying experiment: rectal distention (RD) and mirt. plus RD. RD was accomplished with 120 ml balloon distension during 60 min to 90 min after a test meal, mirt. was administered 90 minutes before the study. The solid gastric emptying was assessed by collecting the gastric chyme every 15 or 30 min from the duodenal cannula for 3 hours after feeding 375 g solid food; the phenol red solution was injected through the duodenal cannula immediately after the food ingestion, small intestinal transit was assessed by the first appearance of phenol red collected from the colonic cannula. The antral and small intestinal contractions were measured by manometry. Colonic transit was assessed by counting the numbers of radiopaque markers from abdominal X-ray films at different time points (2, 4, 6 hours after inserting the markers via the colon cannula). Results: 1) Mirt. accelerated gastric emptying during the entire 3 hours in normal dogs, the gastric emptying was increased from 25.6±6.5% to 43.0±5.5% at 60 min (P < 0.01), 53.1±5.8% to 73.4±5.7% at 120 min (P=0.02) and 68.9±6.3% to 81.1±6.1% (P=0.03) at 180 min. Moreover, mirt. accelerated delayed gastric emptying induced by RD from 45 min to 180 min after the meal (P < 0.04). 2) Mirt. enhanced antral contractions from 12.5±1.9 to 22.5±4.6 (P=0.06). 3) No significant changes were noted on the small intestinal contractions and transit with mirt. (P > 0.1). 4). Mirt. accelerated colonic transit at 2 and 4 hours but not 6 hours. The geometric center was increased from 1.9±0.6 to 3.0±0.5, 3.9±0.5 to 4.7±0.1 at 2 and 4 hours respectively (P=0,04 vs. corresponding control). Conclusion: Mirt. improves gastric and colonic motility and may have a therapeutic potential for gastrointestinal motility disorders.