Tolerance to the mydriatic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine in mice

An increase in the use of opioid derivatives in the treatment of pain syndrome in clinical practice, and especially in the treatment of cancer, has added impetus to the search for an agent which does not induce tolerance and cross-tolerance to other opiodis. The mydriatic effect of opioids in mice, the correlation between analgesia and mydriasis, and tolerance to the analgesic effect of morphine in mice were evaluated previously. In the present work, tolerance to the mydriatic effect of four agonist-antagonists and cross-tolerance to morphine were examined. Measurement of the pupillary diameter was performed using a binocular operating microscope. Tolerance and cross-tolerance to morphine were developed following a chronic use of buprenorphine, nalbuphine, and cyclorphan. After chronic injection of butorphanol, no tolerance or cross-tolerance to morphine was observed.