Antagonism of the analgesic effect of opioid and non-opioid agents by p-chlorophenylalanine (PCPA).

Abstract

The ability of p-chlorophenylalanine (PCPA), an inhibitor of serotonin (5HT) biosynthesis to antagonize the antinociceptive effects of three classes of analgesics: opiates agonist (morphine), opiate agonist-antagonist (pentazocine) and non-steroid anti-inflammatory (aspirin and clonixin) were evaluated using the rat yeast paw test. The analgesic effect of equipotent doses of each of these drugs was abolished 48 h after PCPA (300 mg/kg i.p.) PCPA (150 mg/kg i.p.) reduced the relative potencies of morphine and aspirin to the same degree. The effect could not be attributed to a hyperalgesia or to an interaction with inflammatory mechanisms. PCPA did not alter the anti-edema activity of clonixin and it blocked morphine-induced increases in reaction times to pressure applied to the non-inflamed paw to the same extent as in the inflamed paw. The serotonin precursor 5-hydroxytryptophan (5HTP, 80 mg/kg i.p.) restored the antinociceptive activity of all four drugs. These results demonstrate serotonin can modulate sensitivity to analgesics with differing mechanisms of action.

• Authors: R I Taber, M B Latranyi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 75 Issue 4 Pg. 215-22 (Nov 05 1981) ISSN: 0014-2999 [Print] Netherlands
• PMID: 6119218 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Analgesics, Opioid
• Anti-Inflammatory Agents
• Morphine
• 5-Hydroxytryptophan
• Aspirin
• Fenclonine
• Pentazocine
• Clonixin

Topics

• 5-Hydroxytryptophan (pharmacology)
• Analgesics (antagonists & inhibitors)
• Analgesics, Opioid (antagonists & inhibitors)
• Animals
• Anti-Inflammatory Agents
• Aspirin (antagonists & inhibitors)
• Clonixin (antagonists & inhibitors)
• Dose-Response Relationship, Drug
• Fenclonine (pharmacology)
• Morphine (antagonists & inhibitors)
• Nociceptors (drug effects)
• Pentazocine (antagonists & inhibitors)
• Rats