Effects of β-funaltrexamine (β-FNA) on morphine dependence in rats and monkeys

Mario D. Aceto, William L. Dewey, P. S. Portoghese, A. E. Takemori

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38 Scopus citations

Abstract

The opioid μ receptor antagonist β-funaltrexamine (β-FNA) blocked the development of physical dependence in rats when infused simultaneously with morphine for 6 days. In addition, β-FNA given s.c. 24 h prior to the initiation and on day 3 of a 6 day period of morphine infusion in rats reduced the development of physical dependence in a dose-dependent manner. In morphine-dependent rhesus monkeys, β-FNA precipitated a prompt and long-lasting withdrawal, which was not reversed within by 30 h by subsequent injections of morphine. In contrast, naloxone-induced withdrawal lasted approximately 90 min. These results provide further evidence that β-FNA is a long-acting antagonist of the opioid μ receptor, and that this receptor has a major role in the development of morphine-induced physical dependence.

Original languageEnglish (US)
Pages (from-to)387-393
Number of pages7
JournalEuropean Journal of Pharmacology
Volume123
Issue number3
DOIs
StatePublished - Apr 29 1986

Bibliographical note

Funding Information:
We thank F.T. Grove, B. Jones and S. Tucker for their excellent technical help and Dr. David Brase for assistance in the preparation of the manuscript. This study was supported by U.S. Public Health Service Grants DA-00289, DA-01533, DA-01647 and contract No. 271-81-3830 from the National Institute on Drug Abuse.

Keywords

  • Irreversible antagonist
  • Monkeys
  • Morphine
  • Naloxone
  • Physical dependence
  • Rats
  • β-Funaltrexamine

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