Nakamura H, Ishii K, Yokoyama Y, Imazu C, Shimoda A, Kadokawa T, Shimizu M
Eur J Pharmacol. 1984 Nov 13;106(2):345-56. doi: 10.1016/0014-2999(84)90722-2.
The site of the analgesic action of AD-1211, the less active stereoisomer, and its pharmacological features were investigated. AD-1211, as well as pentazocine and morphine, blocked the reflex hypertension caused by injection of both bradykinin and bradykinin plus PGE1 into the splenic artery of dogs. In the rat or mouse writhing test, the analgesic activity of AD-1211 after intraperitoneal and intracisternal administration was equal to and more than 40 times, respectively, that after intravenous administration. The analgesic activity of AD-1211, unlike that of pentazocine and morphine, was incompletely reversed by naloxone and was not attenuated even by its repeated administration for 7 days in the mouse writhing and tail pressure test, respectively. AD-1211, unlike pentazocine and/or morphine, lacked some effects on central nervous, respiratory and cardiovascular function in conscious animals. These results demonstrate that AD-1211 produces its analgesic action through a central mechanism but lacks some of the common pharmacological actions shown by morphine-like analgesics.
对活性较低的立体异构体AD - 1211的镇痛作用部位及其药理学特性进行了研究。AD - 1211与喷他佐辛和吗啡一样，能阻断向犬脾动脉注射缓激肽以及缓激肽加前列腺素E1所引起的反射性高血压。在大鼠或小鼠扭体试验中，腹腔注射和脑池内注射后AD - 1211的镇痛活性分别相当于静脉注射后的镇痛活性，且分别比静脉注射后的镇痛活性高40倍以上。与喷他佐辛和吗啡不同，AD - 1211的镇痛活性不能被纳洛酮完全逆转，并且在小鼠扭体试验和尾部压痛试验中，即使连续7天重复给药，其镇痛活性也不会减弱。与喷他佐辛和/或吗啡不同，AD - 1211对清醒动物的中枢神经、呼吸和心血管功能没有某些作用。这些结果表明，AD - 1211通过中枢机制产生镇痛作用，但缺乏吗啡样镇痛药所具有的一些常见药理作用。
