• DOI:10.1213/01.ANE.0000154303.93909.A3
• Corpus ID: 23861688

The Effects of the Tramadol Metabolite O-Desmethyl Tramadol on Muscarinic Receptor-Induced Responses in Xenopus Oocytes Expressing Cloned M1 or M3 Receptors

@article{Nakamura2005TheEO,
  title={The Effects of the Tramadol Metabolite O-Desmethyl Tramadol on Muscarinic Receptor-Induced Responses in Xenopus Oocytes Expressing Cloned M1 or M3 Receptors},
  author={Motohiro Nakamura and Kouichiro Minami and Yasuhito Uezono and Takafumi Horishita and Junichi Ogata and Munehiro Shiraishi and Takashi Okamoto and Tadanori Terada and Takeyoshi Sata},
  journal={Anesthesia \& Analgesia},
  year={2005},
  volume={101},
  pages={180-186}
}

• Motohiro Nakamura, K. Minami, +6 authors T. Sata
• Published 1 July 2005
• Biology
• Anesthesia & Analgesia

O-desmethyl tramadol is one of the main metabolites of tramadol. It has been widely used clinically and has analgesic activity. Muscarinic receptors are involved in neuronal functions in the brain and autonomic nervous system, and much attention has been paid to these receptors as targets for analgesic drugs in the central nervous system. We have reported that tramadol inhibits the function of type-1 muscarinic (M1) receptors and type-3 muscarinic (M3) receptors, suggesting that muscarinic receptors are sites of action of tramadol. However, the effects of O-desmethyl tramadol on muscarinic receptor functions have not been studied in detail. In this study, we investigated the effects of O-desmethyl tramadol on M1 and M3 receptors, using the Xenopus oocyte expression system. O-desmethyl tramadol (0.1–100 &mgr;M) inhibited acetylcholine (ACh)-induced currents in oocytes expressing the M1 receptors (half-maximal inhibitory concentration [IC50] = 2 ± 0.6 &mgr;M), whereas it did not suppress ACh-induced currents in oocytes expressing the M3 receptor. Although GF109203X, a protein kinase C inhibitor, increased the ACh-induced current, it had little effect on the inhibition of ACh-induced currents by O-desmethyl tramadol in oocytes expressing M1 receptors. The inhibitory effect of O-desmethyl tramadol on M1 receptor was overcome when the concentration of ACh was increased (KD with O-desmethyl tramadol = 0.3 &mgr;M). O-desmethyl tramadol inhibited the specific binding of [3H]quinuclidinyl benzilate ([3H]QNB) to the oocytes expressed M1 receptors (IC50 = 10.1 ± 0.1 &mgr;M), whereas it did not suppress the specific binding of [3H]QNB to the oocytes expressed M3 receptors. Based on these results, O-desmethyl tramadol inhibits functions of M1 receptors but has little effect on those of M3 receptors. This study demonstrates the molecular action of O-desmethyl tramadol on the receptors and may help to explain its neural function.