Action of opioid agonist-antagonist drugs on the pupil and nociceptive responses in mice

Opioid derivatives with mixed agonist-antagonist activities are becoming increasingly more popular in analgesia. We tested the mydriatic and analgesic activity of morphine in mice in comparison with similar effects of three agonist-antagonist agents: buprenorphine, butorphanol and nalbuphine. We also examined the antagonistic action of these three drugs by evaluating the analgesia and mydriasis in animals pretreated with morphine. The analgesic effect was assayed using the hot plate method while the pupillary responses were measured with a binocular operating microscope. Morphine produced dose-dependent mydriasis and analgesia in mice. The morphine-type agent buprenorphine and two nalorphine-type agonistantagonists, butorphanol and nalbuphine, caused agonistic mydriatic and analgesic effects, usually less effective then morphine. Buprenorphine proved to have higher agonist activity than butorphanol and nalbuphine. The difference between butorphanol and nalbuphine was not statistically significant. A correlation between the mydriatic and the analgesic activity, known to exist among oploid derivatives with agonist activity only, was also demonstrated in the three investigated agonist-antagonist agents. Morphine-induced mydriasis and analgesia were reversed by all three agonist-antagonist drugs, but buprenorphine is a significantly weak antagonist in comparison with butorphanol and nalbuphine. An antagonistic property (antimydriatic and antianalgesic effects after pretreatment with morphine) of both nalorphine-type investigated drugs was not statistically significant, except for the antianalgesic effect of nalbuphine in doses 1 and 3 mg·kg ^-1 which was higher in comparison with butorphanol.