Pharmacological properties of newly synthesized derivatives of (-)-6 beta-acetylthionormorphine and their interactions with opioid receptors.

1. Some pharmacological properties of newly synthesized derivatives of (-)-6 beta-acetylthionormorphine, AcS-morphine (KT-88), KT-89 and KT-90 and their interactions with opioid receptors were studied. 2. AcS-morphine was about twice as potent as morphine in the inhibitory action of the twitch response of the guinea-pig ileal preparation to electrical stimulation and about 5 times as potent as morphine in the analgesic action in the rats. Both the effects of AcS-morphine were inhibited by naloxone, suggesting that the site of action of AcS-morphine is mu-receptors. 3. Analgesic activities of KT-89 and KT-90 were about 6 and 10 times as potent as morphine in an acetic acid-induced writhing test and about 4 and 5 times as potent as in a pressure test. 4. As the analgesic action of KT-90 was antagonized by norbinaltorphimine, the site of action of KT-90 is concluded to be kappa-receptors. Furthermore, KT-89 and KT-90 behaved as antagonists on mu-receptors. 5. The present results suggest that AcS-morphine which is N-methyl derivative, as well as morphine, has a selectively high affinity to mu-receptors, and that KT-89 and KT-90 which are N-cyclopropylmethyl derivatives have nonselectively high affinities to mu-, kappa- and delta-receptors.