Takayanagi I, Konno F, Goromaru N, Koike K, Kanematsu K, Fujii I, Togame H
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Arch Int Pharmacodyn Ther. 1988 Jul-Aug;294:71-84.
Some pharmacological properties of a newly synthesized morphine derivative, (-)-6 beta-acetylthiomorphine (AcS-morphine) were studied. 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. AcS-morphine, however, was 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. It is interesting that 6 beta-isomer of AcS-morphine is 5 times as potent as 6 alpha-OH isomer of morphine in the analgesic action, because 6 alpha-OH isomer of morphine is much more potent than that of 6 beta-OH isomer. The effects of AcS-morphine on the specific binding of [3H]-naloxone, [3H]-ethylketocyclazocine and [3H]-D-Ala2-D-Leu5-enkephalin to the membrane fractions from the rat brain were tested. AcS-morphine was about 5 times as potent as morphine in its interactions with opioid receptors, as determined by the binding assay. AcS-morphine, as well as morphine, had a selectively high affinity to mu-receptors. The "sodium effect" and the "GTP effect" of AcS-morphine were almost the same as those of morphine. The dependence liability of AcS-morphine was preliminary tested in the guinea-pig ileal preparations treated with a high concentration of AcS-morphine for 24 hr. Results suggested that AcS-morphine is weaker than morphine in its dependence liability, though it seems almost certain that AcS-morphine does have this liability.
