Central actions of AD-1211, an analgesic lacking common opiate features.

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.