[Enkephalinase mechanisms of tolerance of analgetic action of opioids. Effects of D-phenylalanine and naloxone].

The paper reviews the data available in the literature and the authors own data demonstrating the differences in the levels of endogenous opioids and in the effects of enkephalinase inhibitor and naloxone in morphine-responsive and morphine-resistant and -tolerant animals. In the morphine-tolerant animals, a single administration of enkephalinase inhibitor or some doses of naloxone was found to produce an analgesic effect leading to a short-term analgesic effect of morphine. Chronic administration of naloxone causing a gradual decrease in and subsequent cessation of its analgesic effect leads to recovery of morphine's analgesic effect in the drug-resistant and -tolerant animals. It is suggested that the morphine-resistant animals have a congenital high activity of enkephalinase, while the drug-tolerant ones have its acquired high activity. Naloxone in certain doses with the high activity of enkephalinase act as its inhibitor, but in high doses acts as its opioid antagonist.