Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects.

Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society
A E BharuchaA R Zinsmeister

Abstract

Alpha-2 adrenergic receptors tonically inhibit colonic motility and the alpha(2)-adrenergic antagonist yohimbine, given intravenously, increased colonic tone in humans. However, the effect of yohimbine on colonic transit in humans is unknown. In this study, 30 healthy volunteers were randomized to yohimbine 16.2 mg p.o. t.i.d. or identical placebo for 7 days. We evaluated gastric emptying, small intestinal, and colonic transit by scinitigraphy, bowel habits, haemodynamics and plasma catecholamines. As cytochrome P450 enzymes metabolize yohimbine, P450 genotypes (CYP2D6 and CYP3A4) were determined in 25 of 30 subjects who consented to genetic studies. The relationship between drug metabolizer status predicted by CYP2D6 and CYP3A4 and effects of yohmibine were assessed. Compared to placebo, yohimbine increased (P < or = 0.02) diastolic blood pressure, plasma noradrenaline concentrations and maximum tolerated volume during the satiation test [yohimbine (1241 +/- 88, mean +/- SEM) vs placebo (1015 +/- 87), P = 0.054]. However, yohimbine did not affect gastrointestinal transit. Based on CYP2D6 and CYP3A4 alleles, seven and 18 subjects were, respectively, extensive (EM) and poor (PM) metabolizers of yohimbine. Compared to EM, PM of y...Continue Reading

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Citations

Oct 19, 2010·Journal of Veterinary Pharmacology and Therapeutics·H K Dimaio KnychS D Stanley
Dec 9, 2014·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·A LoavenbruckA E Bharucha
Sep 16, 2014·Langmuir : the ACS Journal of Surfaces and Colloids·Dongmei CuiSongqin Liu

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