Long-lasting effects of methocinnamox on opioid self-administration in rhesus monkeys

David R. Maguire, Lisa R Gerak, James H. Woods, Stephen M. Husbands, Alex Disney, Charles P France

Research output: Contribution to journalArticle

Abstract

Opioid abuse remains a serious public health challenge, despite the availability of medications that are effective in some patients (naltrexone, buprenorphine, and methadone). This study explored the potential of a pseudoirreversible mu-opioid receptor antagonist [methocinnamox (MCAM)] as a treatment for opioid abuse by examining its capacity to attenuate the reinforcing effects of mu-opioid receptor agonists in rhesus monkeys. In one experiment, monkeys responded for heroin (n 5 5) or cocaine (n 5 4) under a fixed-ratio schedule. Another group (n 5 3) worked under a choice procedure with one alternative delivering food and the other alternative delivering the mu-opioid receptor agonist remifentanil. A third group (n 5 4) responded for food and physiologic parameters were measured via telemetry. The effects of MCAM were determined in all experiments and, in some cases, were compared with those of naltrexone. When given immediately before sessions, naltrexone dose-dependently decreased responding for heroin and decreased choice of remifentanil while increasing choice of food, with responding returning to baseline levels 1 day after naltrexone injection. MCAM also decreased responding for heroin and decreased choice of remifentanil while increasing choice of food; however, opioid-maintained responding remained decreased for several days after treatment. Doses of MCAM that significantly decreased opioid-maintained responding did not decrease responding for cocaine or food. MCAM did not impact heart rate, blood pressure, body temperature, or activity at doses that decreased opioid self-administration. Because MCAM selectively attenuates opioid self-administration for prolonged periods, this novel drug could be a safe and effective alternative to currently available treatments for opioid abuse.

Original languageEnglish (US)
Pages (from-to)88-99
Number of pages12
JournalJournal of Pharmacology and Experimental Therapeutics
Volume368
Issue number1
DOIs
StatePublished - Jan 1 2019

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Self Administration
Macaca mulatta
Opioid Analgesics
Naltrexone
mu Opioid Receptor
Heroin
Food
Cocaine
Buprenorphine
Telemetry
Narcotic Antagonists
Methadone
methocinnamox
Body Temperature
Haplorhini
Appointments and Schedules
Therapeutics
Public Health
Heart Rate
Blood Pressure

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Long-lasting effects of methocinnamox on opioid self-administration in rhesus monkeys. / Maguire, David R.; Gerak, Lisa R; Woods, James H.; Husbands, Stephen M.; Disney, Alex; France, Charles P.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 368, No. 1, 01.01.2019, p. 88-99.

Research output: Contribution to journalArticle

Maguire, David R. ; Gerak, Lisa R ; Woods, James H. ; Husbands, Stephen M. ; Disney, Alex ; France, Charles P. / Long-lasting effects of methocinnamox on opioid self-administration in rhesus monkeys. In: Journal of Pharmacology and Experimental Therapeutics. 2019 ; Vol. 368, No. 1. pp. 88-99.
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