IN VITRO EVALUATION OF THE EFFECT OF OPIOID ANTAGONIST, N‐METHYLNALTREXONE ON MOTILITY IN THE EQUINE JEJUNUM AND PELVIC FLEXURE

While potent analgesic agents, opioids reduce intestinal transport in the intestine, thereby increasing transit times and the potential for impaction colic. Methylnaltrexone is an opioid receptor antagonist which does not cross the blood-brain barrier, does not reverse the analgesic effects of morphine, and directly stimulates isolated smooth muscle strips in humans. Objective: To determine if N-methynaltrexone has an effect on contractile activity of the equine jejunum and pelvic flexure. Study Design: In vitro investigation using isolated circular smooth muscle strips. Animals: 8 adult horses (n=200 muscle strips). Methods: Increasing concentrations of N-methylnaltrexone were added to tissue baths in the range of 1×10−9 M to 1×10−5 M, and contractile responses were recorded for 3 minutes. Data was analyzed using a repeated measures ANOVA with statistical significance as P<0.05. Results: The administration of N-methylnaltrexone significantly increased the contractile frequency and amplitude at all concentrations relative to baseline (P <0.0001) for the jejunum. The response was greatest at 1×10−7 M (P=0.0005) with a mean difference from baseline of 0.341 mg/cm2. The highest concentration evaluated (1×10−5 M) had a mean contractile strength of 0.206 mg/cm2 which was significantly greater than baseline activity (P=0.04). A significant increase in contractile activity for the colon was detected at 3×10−6 M (P=0.027) and 1×10−5 M (P=0.002). Clinical Relevance: Potentially, this agent could be used in conjunction with morphine to provide more potent and effective analgesia without compromising intestinal function.