INTERACTIONS BETWEEN NARCOTIC AGONISTS, PARTIAL AGONISTS AND ANTAGONISTS EVALUATED BY SCHEDULE-CONTROLLED BEHAVIOR

Abstract

The effects of morphine, butorphanol, cyclazocine, ketocyclazocine, ethylketocyclazocine and SKF-10,047 [N-allylnorphenazocine] were tested, alone and in conjunction with naloxone or naltrexone, in rats responding under a fixed-interval, 5 min schedule of food presentation. Except for naloxone and naltrexone, all drugs decreased the average rate of responding in a dose-dependent manner. The rate-decreasing effects of morphine were markedly antagonized by naltrexone, while the effects of SKF-10,047 or high doses of cyclazocine were not antagonized by naltrexone or naloxone. Naltrexone and naloxone were able to antagonize the effects of butorphanol, ketocyclazocine, ethylketocyclazocine and low doses of cyclazocine, but the drugs were considerably more difficult to antagonize than was morphine. The interactions between the drugs and the narcotic antagonists allow the classification of the drugs into 3 groups, based on a marked shift, a moderate shift or no shift in the dose-response curve. This classification is consistent with the hypothesis of Martin regarding distinct receptors for morphine and related drugs (.mu. agonists), ketocyclazocine and ethlketocyclazocine (.kappa. agonists) and SKF-10,047 (.sigma. agonist).