Objective-To determine the response to neostigmine of the contractile activity of the jejunum and pelvic flexure and the effects of a continuous rate infusion (CRI) of neostigmine in horses. Animals-7 adult horses and tissue from 12 adult horses. Procedures-A CRI of neostigmine (0.008 mg/kg/h) or placebo was administered to 6 horses in a crossover study design. Gastric emptying was evaluated by the acetaminophen test. The frequency of defecation and urination and the consistency and weight of feces were recorded throughout the experiment. The effect of neostigmine on smooth muscle contractile activity was evaluated in tissues from the jejunum and pelvic flexure. The effect of neostigmine and acetylcholine after incubation with muscarinic receptor antagonists (atropine and DAU 5884) and an acetylcholinesterase inhibitor (edrophonium) was also investigated in vitro. Results-No difference was observed between neostigmine and placebo for time to reach peak plasma acetaminophen concentration and absorption rate constant. A CRI of neostigmine increased fecal production and frequency of urination. Neostigmine induced a dose-dependent increase of contractile amplitude in jejunum and pelvic flexure muscle strips. Incubation of muscle strips with atropine and DAU 5884 inhibited the response to acetylcholine and neostigmine. Incubation of smooth muscle strips from the jejunum with edrophonium increased the response to acetylcholine and had no effect on the response to neostigmine in vitro. Conclusions and Clinical Relevance-A CRI of neostigmine increased fecal production and urination frequency in horses. A CRI of neostigmine did not decrease gastric emptying. Neostigmine stimulated contractile activity of jejunum and pelvic flexure smooth muscle strips in vitro.

Objective-To determine the effects of domperidone on in vivo and in vitro measures of gastrointestinal tract motility and contractility in healthy horses. Sample-18 adult horses and tissue samples from an additional 26 adult horses. Procedures-Domperidone or placebo paste was administered to healthy horses in a 2-period crossover study. Gastric emptying was evaluated after oral administration of domperidone paste (1.1 or 5.0 mg/kg) or placebo paste by means of the acetaminophen absorption test in 12 horses. Frequency of defecation, weight of feces produced, fecal moisture, and stomach-to-anus transit time of microspheres were evaluated after administration of domperidone paste (1.1 mg/kg) or placebo paste in 6 horses. The effect of domperidone on smooth muscle contractile activity in samples of duodenum, jejunum, ileum, or colon obtained from 26 horses immediately after euthanasia (for nonsystemic medical problems) was investigated. Results-Oral administration of 5.0 mg of domperidone/kg increased peak plasma acetaminophen concentration and area under the curve, indicating increased gastric emptying. Administration of 1.1 mg of domperidone/kg had no effect on gastric emptying, transit time, defecation frequency, or amount and moisture of excreted feces. Contractile activities of circular and longitudinal muscle strips from the duodenum, jejunum, ileum, or colon were not altered by domperidone. Dopamine increased contractile activity of longitudinal muscle strips but not that of circular muscle strips from the midjejunum. Domperidone decreased the dopamine-induced contractile activity of midjejunal longitudinal muscle strips. Conclusions and Clinical Relevance-The potential beneficial effects of domperidone in horses with ileus need to be evaluated in horses with decreased gastric emptying or adynamic ileus.