Dextromethorphan potentiates morphine-induced antinociception at both spinal and supraspinal sites but is not related to the descending serotoninergic or adrenergic pathways.

Abstract

Morphine is a strong and widely used opioid analgesic in pain management, but some adverse effects limit its clinical use at high doses. The clinically available non-opioid antitussive, dextromethorphan (DM) can potentiate the analgesic effect of morphine and decrease the dose of morphine in acute postoperative pain. However, the mechanism underlying this synergistic phenomenon is still not clear. To examine if the potentiation by DM occurs through the descending pain-inhibitory pathways, ketanserin (a 5-HT2 receptor antagonist) and yohimbine (an alpha2-adrenergic receptor antagonist) were employed and found to have no significant effect on the potentiation by DM. Using local delivery of drugs in rats in the present study, potentiation of morphine-induced antinociception by DM was observed via both intrathecal and intracerebroventricular routes, suggesting that both spinal and supraspinal sites are involved. This suggests that the potentiation of morphine-induced antinociception by DM is not mediated by the serotoninergic or adrenergic descending pain-inhibitory pathways. The present results are consistent with findings in clinical studies, which showed that DM can effectively decrease the consumption of morphine in patients suffering from pain. Since DM has excellent clinical potential as a synergistic agent with morphine, further investigating and clarifying the possible pharmacological mechanism of DM are of great importance for future studies.

• Authors: Lok-Hi Chow, Eagle Y-K Huang, Shung-Tai Ho, Shen-Kou Tsai, Pao-Luh Tao
• Journal: Journal of biomedical science (J Biomed Sci) 2004 Nov-Dec Vol. 11 Issue 6 Pg. 717-25 ISSN: 1021-7770 [Print] England
• PMID: 15591767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2004 National Science Council, ROC and S. Karger AG, Basel

Chemical References

• Adrenergic Agents
• Adrenergic alpha-Antagonists
• Analgesics, Opioid
• Receptors, Opioid, mu
• Serotonin Antagonists
• Yohimbine
• Serotonin
• Dextromethorphan
• Morphine
• Ketanserin

Topics

• Adrenergic Agents (pharmacology)
• Adrenergic alpha-Antagonists (pharmacology)
• Analgesics, Opioid (pharmacology)
• Animals
• Back
• Dextromethorphan (pharmacology)
• Drug Synergism
• Injections, Spinal
• Ketanserin (pharmacology)
• Kinetics
• Male
• Morphine (pharmacology)
• Pain (drug therapy)
• Pain Measurement
• Protein Binding
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid, mu (metabolism)
• Serotonin (metabolism)
• Serotonin Antagonists (pharmacology)
• Spinal Cord (drug effects)
• Time Factors
• Yohimbine (pharmacology)