methylnaltrexone and Body-Weight

Among the many analgesic agents available, buprenorphine appears to be the analgesic used most often in rabbits. Unfortunately, deleterious side effects of opioids, such as gastrointestinal stasis and anorexia, may discourage the use of these agents. Methylnaltrexone is a peripheral opioid antagonist that ameliorates opioid-induced gastrointestinal stasis in others species yet preserves the analgesic effects of buprenorphine. We evaluated whether methylnaltrexone reversed buprenorphine-induced gastrointestinal stasis in 8 healthy male New Zealand White rabbits. To measure gastrointestinal transit time, each rabbit received 20 barium-filled spheres through an orogastric tube. Rabbits then received 4 treatments in random order: buprenorphine (0.05 mg/kg SC), methylnaltrexone (1 mg/kg SC), both agents combined (B+M), or normal saline (control) every 12 h for 2 d. Fecal production was measured every 6 h, and water and food consumption, and body weight, were measured daily, for 5 d after each treatment. The time to appearance of the first sphere was significantly longer for buprenorphine group than for control and methylnaltrexone groups. Daily fecal output was lowest for buprenorphine and B+M, intermediate for control, and highest for methylnaltrexone. Water and food consumption were lower for groups buprenorphine and B+M than for control and methylnaltrexone. Body weight was not affected. In conclusion, treatment with buprenorphine 0.05 mg/kg BID for 2 d in healthy rabbits decreased food and water consumption, prolonged gastrointestinal transit time and decreased the fecal output. Coadministration of methylnaltrexone at 1 mg/kg did not alleviate these negative side effects.

Topics: Analgesics, Opioid; Animals; Body Weight; Buprenorphine; Drug Therapy, Combination; Feces; Gastrointestinal Transit; Laboratory Animal Science; Male; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds; Rabbits

Rats implanted for 5 days with a morphine pellet were dosed once with naltrexone (subcutaneous, s.c.) or methylnaltrexone (intraventricular, i.c.v.). Then the rats were observed for several somatic signs of precipitated withdrawal and tested for aversion to the place of the withdrawal. The two antagonist treatments produced different withdrawal syndromes, but both were associated with a place aversion which followed a simple monophasic function of the dose of antagonist. More importantly, there was an absence of any overall relation between individual withdrawal signs (jumping, writhing, shaking, diarrhea, and weight loss) and the aversive effect seen. It was concluded, therefore, that the motivational impact of opiate abstinence is not always addressed in conventional models of withdrawal.

Topics: Animals; Avoidance Learning; Behavior, Animal; Body Weight; Dose-Response Relationship, Drug; Drug Implants; Male; Morphine; Motivation; Naltrexone; Quaternary Ammonium Compounds; Rats; Rats, Inbred Strains; Substance Withdrawal Syndrome