Comparison of buprenorphine and methadone effects on opiate self-administration in primates.
The effects of ascending and descending doses of buprenorphine (0.014-0.789 mg/kg/day) and methadone (0.179-11.86 mg/kg/day) on opiate and food intake were studied in Macaque monkeys over 195 to 245 days. Food (1-g banana pellets) and i.v. drug self-administration (heroin 0.01 or 0.02 mg/kg/injection or Dilaudid 0.02 mg/kg/injection) were maintained on a second-order schedule of reinforcement [FR 4 (VR 16:S)]. Buprenorphine (0.282-0.789 mg/kg/day) produced a significant suppression of opiate self-administration at 2.5 to 7 times the dose shown to be effective in human opiate abusers (P less than .05-.001). Methadone (1.43-11.86 mg/kg/day) did not suppress opiate self-administration in four of five monkeys across a dose range equivalent to 100 to 800 mg/day in man. The distribution of opiate self-administration across drug sessions did not account for the absence of methadone suppression as monkeys took 43% of the total daily opiate injections during the first daily drug session, 2.5 hr after methadone administration. During buprenorphine maintenance, food intake remained stable or increased significantly above base-line levels. Methadone maintenance was associated with significant decrements in food intake in four of five monkeys. Buprenorphine appeared to be significantly more effective in suppressing opiate self-administration than methadone across the dose range studied. Buprenorphine had none of the toxic side effects (seizures, respiratory depression, profound psychomotor retardation) associated with high doses of methadone over 6 to 8 months of daily drug treatment. These data are consistent with clinical studies of buprenorphine effects on heroin self-administration in human opiate addicts.
D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage* / Q000627:therapeutic use; D003864:Depression, Chemical; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000187:drug effects; D003932:Heroin / Q000008:administration & dosage; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage; D008253:Macaca mulatta; D008254:Macaca nemestrina; D008691:Methadone / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D009019:Morphinans / Q000008:administration & dosage*; D009293:Opioid-Related Disorders / Q000534:rehabilitation*; D012646:Self Administration
D009019:Morphinans; D002047:Buprenorphine; D003932:Heroin; D004091:Hydromorphone; D008691:Methadone