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Research ArticleArticle

ALTERATION OF ANALGESIC RECEPTORANTAGONIST INTERACTION INDUCED BY MORPHINE

A. E. TAKEMORI, TETSUO OKA and NAOKO NISHIYAMA
Journal of Pharmacology and Experimental Therapeutics August 1973, 186 (2) 261-265;
A. E. TAKEMORI
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TETSUO OKA
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NAOKO NISHIYAMA
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Abstract

The narcotic antagonist, naloxone, antagonized much more effectively the analgesic effects of morphine in mice whiCh were treated previously with morphine than in control mice. Mice were pretreated with a >ED99 dose (2 mg/kg) of morphine hydrochloride and after two hours, when the analgesic effect of morphine was no longer evident, doseresponse curves for morphine and the apparent pA2 for morphine-naloxone were determined with these mice. Naloxone shifted the dose-response curves much more to the right when pretreated mice were used and the apparent pA2, shifted significantly from 6.96 to 7.30. The "affinity constant" of naloxone for the analgesic receptor thus increased from 9.12 x 106 to 2.0 x 107 liters/mol when the mice were exposed to one acute injection of morphine. This alteration of the apparent pA2 lasted from 24 hours to 4 days. Pretreatment with pentazocine did not produce similar changes. It is suggested that morphine causes a change in the structure of the receptor such that the affinity of the receptor for narcotic antagonists is increased. In addition, the interaction of analgesic receptors with morphine and pentazocine appears to differ.

Footnotes

    • Received October 30, 1972.
    • Accepted April 9, 1973.
  • © 1973 by The Williams & Wilkins Co.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 186, Issue 2
1 Aug 1973
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Research ArticleArticle

ALTERATION OF ANALGESIC RECEPTORANTAGONIST INTERACTION INDUCED BY MORPHINE

A. E. TAKEMORI, TETSUO OKA and NAOKO NISHIYAMA
Journal of Pharmacology and Experimental Therapeutics August 1, 1973, 186 (2) 261-265;

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Research ArticleArticle

ALTERATION OF ANALGESIC RECEPTORANTAGONIST INTERACTION INDUCED BY MORPHINE

A. E. TAKEMORI, TETSUO OKA and NAOKO NISHIYAMA
Journal of Pharmacology and Experimental Therapeutics August 1, 1973, 186 (2) 261-265;
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