Dose-related antagonism of the emetic effect of morphine by methylnaltrexone in dogs.

Opioids administered to produce analgesia cause unwanted emesis in patients (incidence 20%-30%, depending on situation). Tests in animals show that quaternary narcotic antagonists like methylnaltrexone (MNTX) do not affect the analgesic potency of morphine, but such compounds have not been examined for their potential to antagonize morphine-induced emesis. To determine the effects of MNTX on emetic response, we assigned 85 dogs to one of 11 groups challenged with morphine alone or morphine and various doses of MNTX IM or i.v. Antagonism of the emetic response was dose related: MNTX, 0.25 mg/kg IM or 0.2 mg/kg i.v., completely blocked the emetic effect of morphine in dogs for approximately 60 minutes. If morphine-induced emesis is mediated by receptors available to a quaternary antagonist (perhaps on the peripheral side of the blood-brain barrier), MNTX may prevent opioid-induced emesis. These data indicate that opioid-induced emesis might be prevented without affecting analgesia.