The tramadol metabolite, O-desmethyl tramadol, inhibits 5-hydroxytryptamine type 2C receptors expressed in Xenopus Oocytes.

Article Details

Citation

Copy to clipboard

Horishita T, Minami K, Uezono Y, Shiraishi M, Ogata J, Okamoto T, Shigematsu A

The tramadol metabolite, O-desmethyl tramadol, inhibits 5-hydroxytryptamine type 2C receptors expressed in Xenopus Oocytes.

Pharmacology. 2006;77(2):93-9. Epub 2006 May 5.

PubMed ID

16679816 [ View in PubMed

]

Abstract

PURPOSE: Tramadol is widely used clinically as an analgesic, yet the mechanism by which it produces antinociception remains unclear. O-Desmethyl tramadol, the main metabolite of tramadol, is a more potent analgesic than tramadol. We reported previously that tramadol inhibits the 5-hydroxytryptamine (5-HT) type 2C receptor (5-HT(2C)R), a G-protein-coupled receptor that is expressed widely within brain and that mediates several effects of 5-HT, including nociception, feeding, and locomotion. The effects of O-desmethyl tramadol on 5-HT(2C)R have not been studied. In this study, we investigated the effect of O-desmethyl tramadol on 5-HT(2C)R expressed in Xenopus oocytes. METHODS: We examined the effect of O-desmethyl tramadol on 5-HT(2C)R using the Xenopus oocyte expression system. Furthermore, we investigated the effects of O-desmethyl tramadol on the binding of [(3)H]5-HT by 5-HT(2C)R. RESULTS: O-Desmethyl tramadol, at pharmacologically relevant concentrations, inhibited 5-HT-evoked Ca(2+)-activated Cl(-) currents in oocytes that expressed 5-HT(2C)R. The inhibitory effect of O-desmethyl tramadol on 5-HT(2C)R was overcome at higher concentrations of 5-HT. Bisindolylmaleimide I (GF109203X), a protein kinase C inhibitor, increased 5-HT-evoked currents but had little effect on the inhibition of 5-HT-evoked currents by O-desmethyl tramadol. O-Desmethyl tramadol inhibited the specific binding of [(3)H]5-HT by 5-HT(2C)R expressed in oocytes. O-Desmethyl tramadol altered the apparent dissociation constant for binding of [(3)H]5-HT by 5-HT(2C)R without changing maximum binding, which indicated competitive inhibition. CONCLUSION: These results suggest that O-desmethyl tramadol inhibits 5-HT(2C)R, which provides further insight into the pharmacological properties of tramadol and O-desmethyl tramadol.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tramadol	5-hydroxytryptamine receptor 2C	Protein	Humans	Unknown	Antagonist	Details