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- W1874341750 abstract "The interactions between the opioid antagonist naloxone and the opioids morphine, buprenorphine and demethoxybuprenorphine ( DMB ), an acid-catalyzed rearrangement product of buprenorphine, were evaluated quantitatively in rats trained to discriminate between saline and 3.0 mg/kg of morphine using a two-choice, shock avoidance procedure. Dose-effect curves for each of the three agonists were determined alone and in the presence of varying doses of naloxone (0.01-1.0 mg/kg). Buprenorphine and DMB produced dose-related increases in morphine-appropriate responding which plateaued over at least a 30-fold dose-range for each drug. On a molar basis, buprenorphine was approximately 140 times and DMB approximately 45 times more potent than morphine. Naloxone produced parallel shifts in the dose-effect curves for morphine, buprenorphine and DMB . Schild plots derived from the relative shifts in the dose-effect curves yielded regression lines with slopes which were not significantly different from -1, consistent with naloxone acting as a competitive antagonist of each of the three opioids. The apparent pA2 values for naloxone were 7.85 +/- 0.36 against morphine, 7.48 +/- 0.16 against buprenorphine and 7.17 +/- 0.27 against DMB . Because the 95% CLs overlapped for morphine and buprenorphine, but not for morphine and DMB , these results are consistent with the interpretation that naloxone is acting at the same receptor in antagonizing morphine and buprenorphine but naloxone may be acting in a more complex manner in antagonizing DMB . The effectiveness of naloxone in antagonizing equieffective doses of morphine (3.0 mg/kg), buprenorphine (0.03 mg/kg) and DMB (0.1 mg/kg) were also evaluated when naloxone was administered either 0 or 30 min after the agonist.(ABSTRACT TRUNCATED AT 250 WORDS)" @default.
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- W1874341750 date "1984-06-01" @default.
- W1874341750 modified "2023-09-25" @default.
- W1874341750 title "Morphine-like discriminative stimulus effects of buprenorphine and demethoxybuprenorphine in rats: quantitative antagonism by naloxone." @default.
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