| Title: |
The Tramadol Metabolite, O-Desmethyl Tramadol, Inhibits 5-Hydroxytryptamine Type 2C Receptors Expressed in Xenopus Oocytes |
| Authors: |
Horishita, Takafumi; Minami, Kouichiro; Uezono, Yasuhito; Shiraishi, Munehiro; Ogata, Junichi; Okamoto, Takashi; Shigematsu, Akio |
| Source: |
Pharmacology ; volume 77, issue 2, page 93-99 ; ISSN 0031-7012 1423-0313 |
| Publisher Information: |
S. Karger AG |
| Publication Year: |
2006 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1159/000093179 |
| Availability: |
https://doi.org/10.1159/000093179; https://www.karger.com/Article/Pdf/93179 |
| Rights: |
https://www.karger.com/Services/SiteLicenses ; https://www.karger.com/Services/SiteLicenses |
| Accession Number: |
edsbas.49F5F0A6 |
| Database: |
BASE |