Opioid agonist and antagonist properties of diastereoisomeric N-tetrahydronoroxymorphones in mice.

Opioid agonist and antagonist properties of diastereoisomeric N-Tetrahydrofurfurylnoroxymorphones, Mr 2096 and Mr 2097 were examined in mice using the hot plate and tail flick tests and on acute dependence. Subcutaneous administrations of Mr 2096, the agonist diastereoisomer and Mr 2097, the antagonist diastereoisomer respectively produced analgesia and hyperalgesia in these tests, confirming the involvement of stereoselective opioid receptors in the regulation of thermonociception. Intracerebroventricular injection of Mr 2096 prolonged the tail flick latency, but that of Mr 2097 was without effect. The analgesic effect of Mr 2096 might be due to mimicking the descending inhibition of nociception and suppression of nociceptive reflexes at the level of spinal cord. The absence of hyperalgesia in the tail flick test following the central administration of Mr 2097 might arise from a rapid fall in concentration at relevant receptor sites and/or absence of a significant effect on the spinal reflex. In mice acutely dependent on morphine, Mr 2096 did not precipitate withdrawal. Mr 2097 behaved as an antagonist, precipitating withdrawal. These experiments indicate that stereoselective opioid receptors are involved in acute withdrawal syndrome. This study further confirms the importance of the steric properties of N-substituted moieties in Tetrahydrofurfurylnoroxymorphones.