Antagonism of alpha 3 beta 4 nicotinic receptors as a strategy to reduce opioid and stimulant self-administration

European Journal of Pharmacology
Stanley D GlickM W Fleck

Abstract

The iboga alkaloid ibogaine and the novel iboga alkaloid congener 18-methoxycoronaridine are putative anti-addictive agents. Using patch-clamp methodology, the actions of ibogaine and 18-methoxycoronaridine at various neurotransmitter receptor ion-channel subtypes were determined. Both ibogaine and 18-methoxycoronaridine were antagonists at alpha 3 beta 4 nicotinic receptors and both agents were more potent at this site than at alpha 4 beta 2 nicotinic receptors or at NMDA or 5-HT(3) receptors; 18-methoxycoronaridine was more selective in this regard than ibogaine. In studies of morphine and methamphetamine self-administration, the effects of low dose combinations of 18-methoxycoronaridine with mecamylamine or dextromethorphan and of mecamylamine with dextromethorphan were assessed. Mecamylamine and dextromethorphan have also been shown to be antagonists at alpha 3 beta 4 nicotinic receptors. All three drug combinations decreased both morphine and methamphetamine self-administration at doses that were ineffective if administered alone. The data are consistent with the hypothesis that antagonism at alpha 3 beta 4 receptors is a potential mechanism to modulate drug seeking behavior. 18-Methoxycoronaridine apparently has greater s...Continue Reading

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Citations

Aug 3, 2005·Cellular and Molecular Neurobiology·John W Daly
Nov 13, 2003·Peptides·Richard J Bodnar, Maria M Hadjimarkou
Apr 2, 2003·Pharmacology, Biochemistry, and Behavior·Caren L SteinmillerStanley D Glick
Aug 5, 2003·Pharmacology, Biochemistry, and Behavior·Isabelle M Maisonneuve, Stanley D Glick
May 24, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·James J CortrightPaul Vezina
May 12, 2006·Substance Abuse : Official Publication of the Association for Medical Education and Research in Substance Abuse·Malcolm S ReidJohn Rotrosen
Nov 10, 2013·PloS One·Tamara AntonioKenneth Alper
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Jun 7, 2011·The International Journal of Biochemistry & Cell Biology·Hugo R AriasKrzysztof Jozwiak
Oct 22, 2008·European Journal of Pharmacology·Stanley D GlickIsabelle M Maisonneuve
Oct 16, 2007·Progress in Neuro-psychopharmacology & Biological Psychiatry·P VezinaW N Green
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Jun 5, 2004·European Journal of Pharmacology·Christopher J PaceMark W Fleck
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