The behavioral effects of the opioid receptor alkylating agent β-funaltrexamine (β-FNA) were assessed in normal (drug-naive) and morphine-dependent rhesus monkeys. In normal monkeys, β-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, β-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, β-FNA (10 mg/kg, s.c. and 0.003 mg, i.c.v.) precipitated severe abstinence which lasted for 3 days. β-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. β-FNA. These data are consistent with the view that β-FNA has reversible opioid agonist and insurmountable mu selective antagonist activity in the rhesus monkey.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1985|
ASJC Scopus subject areas
- Molecular Medicine