Abstract
The effect of combinations of morphine with methadone, pentazocine and nalorphine on acetic acid-induced stretching in mice has been studied to clarify the nature of the analgesic action of the opioid antagonists. The acetic acid test was found to be equally sensitive to the effects of morphine and nalorphine and less variable than the phenylquinone test. Combinations of methadone or pentazocine with morphine produced summative effects; combinations of morphine and nalorphine, however, did not. The results of the morphine-pentazocine and morphine-nalorphine combination studies were similar to those reported for the analgesic effects of these combinations in man. The morphine-nalorphine interactions produced results in general agreement with a model of competitive dualism. According to this model, nalorphine would be viewed as a partial agonist having high affinity and moderate intrinsic activity for the morphine analgesic receptor. Additional support for the concept of a common analgesic receptor mechanism for morphine and nalorphine was found in experiments showing that morphine-tolerant mice were cross-tolerant to nalorphine and that naloxone, a pure opioid antagonist, blocked the stretching inhibitory effects of morphine and nalorphine to the same extent. The difference found between nalorphine and pentazocine interactions with morphine probably reflects the greater antagonistic potency or higher affinity of nalorphine for the opioid analgesic receptor. In contrast to previous studies, reserpine-like drugs failed to antagonize either morphine or nalorphine analgesia. The validity of selective antagonism of stretching as a measure of clinical analgesia was further discussed.
Footnotes
- Received October 30, 1968.
- Accepted May 13, 1969.
- © 1969, by The Williams & Wilkins Company
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