JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Heishman, S. J.
Right arrow Articles by Liebson, I. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Heishman, S. J.
Right arrow Articles by Liebson, I. A.

Acute opioid physical dependence in humans: effect of varying the morphine-naloxone interval. I

SJ Heishman, ML Stitzer, GE Bigelow and IA Liebson

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Acute opioid physical dependence refers to the withdrawal symptoms precipitated by an opioid antagonist administered after a single dose or short-term infusion of an opioid agonist. This phenomenon is particularly interesting given that the abstinence syndrome has generally been thought to develop only after chronic exposure to opioid agonists. The purpose of this study was to determine the minimum time after agonist administration when antagonist-precipitated withdrawal could be observed. Naloxone (10 mg/70 kg) was administered i.m. either 0, 15, 45 or 90 min after single i.m. injections of morphine (18 mg/70 kg) in five nondependent male opiate users. Physiological and subjective report measures revealed no effect of morphine or naloxone at the 0 and 15 min morphine-naloxone interval conditions; however, before the naloxone challenge 45 and 90 min post-morphine, agonist effects (e.g., miosis, respiratory depression and good drug effect subjective ratings) were clearly evident. Naloxone reversed these effects to premorphine levels and simultaneously precipitated subjective symptoms and observer rated signs of opiate withdrawal. Thus, this study showed that antagonist-precipitated withdrawal in humans was first observed 45 min after agonist administration. Further, the onset of naloxone-precipitated withdrawal effects closely paralleled the onset of morphine agonist effects. The results of this study suggest that adaptational changes underlying the development of physical dependence begin within minutes after acute exposure to an opiate.

Volume 250, Issue 2, pp. 485-491, 08/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
J. Neurophysiol.Home page
M. C. Borras, L. Becerra, A. Ploghaus, J. M. Gostic, A. DaSilva, R. G. Gonzalez, and D. Borsook
FMRI Measurement of CNS Responses to Naloxone Infusion and Subsequent Mild Noxious Thermal Stimuli in Healthy Volunteers
J Neurophysiol, June 1, 2004; 91(6): 2723 - 2733.
[Abstract] [Full Text] [PDF]


Home page
Behav Cogn Neurosci RevHome page
T. H. Kelly, W. W. Stoops, A. S. Perry, M. A. Prendergast, and C. R. Rush
Clinical Neuropharmacology of Drugs of Abuse: A Comparison of Drug-Discrimination and Subject-Report Measures
Behav Cogn Neurosci Rev, December 1, 2003; 2(4): 227 - 260.
[Abstract] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
D. A. White and S. G. Holtzman
Acute Opioid Pretreatment Potentiates Naltrexone-Induced Drinking Suppression in Water-Deprived Rats
J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 156 - 164.
[Abstract] [Full Text]


Home page
J. Pharmacol. Exp. Ther.Home page
M. K. Greenwald, M. L. Stitzer, and K. A. Haberny

J. Pharmacol. Exp. Ther., June 1, 1997; 281(3): 1154 - 1163.
[Abstract] [Full Text]




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
 Molecular Interventions Drug Metabolism and Disposition

Copyright © 1989 by the American Society for Pharmacology and Experimental Therapeutics.