Time course of antagonism of morphine antinociception by intracerebroventricularly administered naloxone in the rat

Frank Porreca, Alan Cowan, Ronald J. Tallarida

Research output: Contribution to journalArticle

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Abstract

This kinetic profile and half-life of naloxone were studied for possible use in determination of pA2 and KB in vivo. Rats were given morphine subcutaneously and after 15 min naloxone or saline, intracerebroventricularly. A further 15 min later, and at 15 min intervals up to 135 min after morphine, the animals were tested for analgesia in the tail flick test. The dose-response curves of the naloxone group were shifted to the right of those for the saline group. Theamount of displacement decreased with time, indicative of the disappearance of naloxone. The graph of log (dose ratio-1) vs. time was linear with negative slope, in agreement with the time-dependent form of the equation for competitive antagonism. From this slope, the half-life of naloxone was calculated to be 13.3 min. These results demonstrate that the time-dependent method is useful in obtaining the kinetics of centrally acting opiate antagonists.

Original languageEnglish (US)
Pages (from-to)55-59
Number of pages5
JournalEuropean Journal of Pharmacology
Volume76
Issue number1
DOIs
StatePublished - Nov 19 1981
Externally publishedYes

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Keywords

  • Half-life
  • Intracerebroventricular administration
  • Morphine
  • Naloxone
  • Pharmacokinetics
  • Time-dependent method

ASJC Scopus subject areas

  • Pharmacology

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