Naltrexone and beta-funaltrexamine antagonism of the antinociceptive and response rate-decreasing effects of morphine, dezocine, and d-propoxyphene

Rationale: Patterns of competitive and insurmountable antagonism provide im portant data to guide the classification and characterization of different types of opioid agonists as well as infer the mechanism of action for agoni sts. Objective: Experiments with the competitive antagonist, naltrexone, an d the insurmountable antagonist, beta-funaltrexamine (beta-FNA), were condu cted to determine whether the antinociceptive and rate-decreasing effects o f the opioid agonists dezocine and d-propoxyphene are 1) mediated through m u opioid receptors in rats, and 2) differ from morphine with respect to rel ative efficacy. Methods: The rat tail-withdrawal assay was used to measure antinociception and a fixed ratio 20 (FR20) schedule of food delivery was u sed to measure rate suppression. Results: Naltrexone (0.01-1.0 mg/kg) was a pproximately equipotent as an antagonist of the antinociceptive and rate-de creasing effects of both morphine and dezocine and as an antagonist of the antinociceptive effects of d-propoxyphene. Naltrexone failed to block the r ate-decreasing effects of d-propoxyphene. beta-FNA (5 and 10 mg/kg) also an tagonized the antinociceptive and rate-decreasing effects of morphine and d ezocine as well as the antinociceptive effects of d-propoxyphene. P-FNA fai led to produce a dose-dependent antagonism of the rate-decreasing effects o f d-propoxyphene. Conclusions: These data suggest that the antinociceptive effects of morphine, dezocine, and cl-propoxyphene and the rate-decreasing effects of morphine and dezocine are mediated through mu opioid receptors. Overall, high doses of beta-FNA produced a greater degree of antagonism of the behavioral effects of dezocine than morphine or d-propoxyphene, confirm ing other reports that dezocine is a lower efficacy agonist than morphine. Additionally, the degree of antagonism produced by beta-FNA was greater for the antinociceptive effects of all three compounds than for the rate-decre asing effects.