ANTINOCICEPTIVE ACTIVITY OF THE NARCOTIC ANTAGONIST ANALGESICS AND ANTAGONISTIC ACTIVTY OF NARCOTIC ANALGESICS IN RODENTS

¹ Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina

By the mouse tail-flick and hot-plate tests, the narcotic antagonist analgesics, pentazocine and cyclazocine, have been shown to possess antinociceptive activity soon after injection. Nalorphine was active in the tail-flick but not in the hot-plate test. Naloxone was active in the tail-ifick test one minute after an i.p. or i.v. injection but was inactive at later times and in the hot-plate test. Morphine was less active at one or five minutes than it was at 20 minutes after the injection. The rate of onset and shortness of duration of the antinociceptive activity of these compounds in the tail-flick test was naloxone > cyclazocine > nalorphine = pentazocine > morphine. Although cyclazocine and naloxone showed antinociceptive activity one minute after an i.p. injection in untreated mice, they antagonized rather than potentiated the analgesic activity of morphine when it was given one minute prior to testing. In mice or rats, an injection of morphine one minute prior to testing antagonized some of the agonistic activity of a dose of morphine given 19 minutes earlier in the tail-flick test. A second injection of morphine or meperidine, but not of levorphanol, antagonized some of the agonistic effects of a previous injection of the same drug in the mouse hot-plate test.