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Open Access Highly Accessed Research article

The enantiomers of tramadol and its major metabolite inhibit peristalsis in the guinea pig small intestine via differential mechanisms

Michael K Herbert1*, Rebecca Weis2 and Peter Holzer3

Author Affiliations

1 Department of Anesthesiology, University of Wuerzburg, Wuerzburg, Germany

2 University of Wuerzburg, Wuerzburg, Germany

3 Research Unit of Translational Neurogastroenterology, Department of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria

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BMC Pharmacology 2007, 7:5  doi:10.1186/1471-2210-7-5

Published: 16 March 2007

Abstract

Background

Inhibition of intestinal peristalsis is a major side effect of opioid analgesics. Although tramadol is an opioid-like analgesic, its effect on gut motility is little known. Therefore, the effect of (+)-tramadol, (-)-tramadol and the major metabolite O-desmethyltramadol on intestinal peristalsis in vitro and their mechanisms of action were examined. Distension-induced peristalsis was recorded in fluid-perfused segments of the guinea pig small intestine. The intraluminal peristaltic pressure threshold (PPT) was used to quantify the motor effects of extraserosally administered drugs.

Results

Racemic tramadol, its (+)- and (-)-enantiomers and the major metabolite O-desmethyltramadol (0.1 – 100 μM) concentration-dependently increased PPT until peristalsis was transiently or persistently abolished. The rank order of potency was (-)-tramadol < (+)-tramadol <O-desmethyltramadol. The peristaltic motor inhibition caused by (+)- and (-)-tramadol was markedly and that of O-desmethyltramadol nearly completely prevented by naloxone, but left unaltered by the 5-hydroxytryptamine receptor antagonists methysergide plus tropisetron. The adrenoceptor antagonists prazosin plus yohimbine reduced the effect of (+)- and (-)-tramadol but not that of O-desmethyltramadol.

Conclusion

The results show that the metabolite O-desmethyltramadol is more potent in inhibiting peristalsis than its parent compound. The action of all tramadol forms depends on opioid receptors, and that of (+)- and (-)-tramadol also involves adrenoceptors.