[Preferential action of eptazocine, a novel analgesic, with opioid receptors in isolated guinea pig ileum and mouse vas deferens preparations].
Actions of eptazocine, a novel analgesic, on isolated smooth muscle preparations were investigated. Eptazocine (10(-5) M) slightly inhibited electrically-driven twitch-tension in guinea pig ileum preparations sensitive to mu- and kappa-agonists, and this effect was antagonized by 10(-7) M naloxone. Eptazocine (10(-5)-10(-4) M) inhibited such an effect by the mu-agonist morphine. In mouse vas deferens preparations having delta-, mu- and kappa-receptors, eptazocine (10(-7) M-) inhibited the twitch-tension in a dose-dependent manner, being hardly inhibited by naloxone. On the other hand, MR-2266 (10(-6) M), a relatively selective kappa-receptor antagonist, inhibited the eptazocine effect. The Ke (equilibrium dissociation constant) value of naloxone against eptazocine was 325 nM and the Ke value of MR-2266 against eptazocine was 33.2 nM, showing that MR-2266 was 9.79-fold more effective than naloxone. These results suggest that eptazocine acted as a mu-receptor antagonist and as a kappa-receptor preferential agonist in isolated smooth muscle preparations.
Tamura
T
T
Central Research Laboratories, Nihon Iyakuhin Kogyo Co., Ltd., Toyama, Japan.
Ogawa
J
J
Taniguchi
T
T
Waki
I
I
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004723:Endorphins / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects
D000700:Analgesics; D004723:Endorphins; D011957:Receptors, Opioid; C033776:eptazocine; D003496:Cyclazocine