Abstract
In a previous study using Nihon Clea (Japan) mice and the abdominal stretching assay, we showed that pretreatment of mice with a single dose of morphine hydrochloride caused a marked increase in the antagonistic effect of naloxone without any apparent change in the analgesic activity of morphine. These results were confirmed using Sasco mice, the tail-flick assay and morphine sulfate. The duration of the increased efficacy of naloxone was >12 < 24 hours. Morphine pretreatment induced the antagonistic potency of other antagonists besides naloxone such as nalorphine and diprenorphine. Pretreatment of mice with other narcotic analgesics such as levorphanol and methadone also induced an increased potency of naloxone. On the other hand, pretreatment with the inactive optical isomer of levorphanol, dextrorphan or naloxone itself did not cause this type of change. It is suggested that this increased efficacy of narcotic antagonist due to narcotic pretreatment might be a sensitive indicator of the initiation and development of tolerance to narcotic analgesics.
Footnotes
- Received October 20, 1973.
- Accepted May 20, 1974.
- © 1974 by The Williams & Wilkins Co.
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