Effects of beta-funaltrexamine in normal and morphine-dependent rhesus monkeys: observational studies.
The behavioral effects of the opioid receptor alkylating agent beta-funaltrexamine (beta-FNA) were assessed in normal (drug-naive) and morphine-dependent rhesus monkeys. In normal monkeys, beta-FNA (10 mg/kg s.c.) produced muscle relaxation and stupor, which could be reversed by the opioid antagonist Win 44,441. Given as a 48-hr pretreatment, beta-FNA antagonized the behavioral effects of acute morphine, but not those of two kappa agonists, ethylketazocine and Mr 2033 (UM 1072). In morphine-dependent monkeys, beta-FNA (10 mg/kg, s.c. and 0.003 mg i.c.v.) precipitated severe abstinence which lasted for 3 days. beta-FNA was more than 13,000 times more potent in precipitating withdrawal after i.c.v. than s.c. administration, whereas naltrexone and Win 44,441 were equipotent by these routes. Deprivation-induced abstinence (14 hr) and withdrawal of similar severity precipitated by naltrexone, Win 44,441 or naloxonazine were suppressed completely by 17.5 mg/kg of morphine. In contrast, 320 mg/kg of morphine failed to suppress completely a withdrawal syndrome of the same severity elicited by s.c. or i.c.v. beta-FNA. These data are consistent with the view that beta-FNA has reversible opioid agonist and insurmountable mu selective antagonist activity in the rhesus monkey.
D000818:Animals; D001392:Azocines / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008253:Macaca mulatta; D009020:Morphine; D009126:Muscle Relaxation / Q000187:drug effects; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced; D019966:Substance-Related Disorders / Q000503:physiopathology*; D013997:Time Factors
D001392:Azocines; D009270:Naloxone; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine; C034643:naloxonazine; C035969:quadazocine