An in vivo assay for the analysis of the biological potency and structure-activity relationships of narcotics: serum testosterone depletion in the male rat.

An in vivo method for the assessment of the agonistic-antagonistic activities and structure-activity relationships of the narcotics is described. The method, which is based on the depletion of serum testosterone levels by the narcotics in the male, satisfies all of the criteria necessary for a valid narcotic assay: 1) The ability of the narcotics to deplete serum testosterone levels is stereospecific; 2) naloxone competitively inhibits their effects; 3) and the relative potencies of the drugs in depressing serum testosterone levels parallels their activity in inhibiting electrically induced contractions of the guinea-pig ileum, the binding of [3H]opiates to "receptors" in rat brain homogenates and their relative effectiveness as analgesics. Although only rats were used in the current studies, the method can be easily adapted for use in any species, including man.