Antagonism of the analgesic effect of opioid and non-opioid agents by p-chlorophenylalanine (PCPA).
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.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000700:Analgesics / Q000037:antagonists & inhibitors*; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors*; D000818:Animals; D000893:Anti-Inflammatory Agents; D001241:Aspirin / Q000037:antagonists & inhibitors; D003002:Clonixin / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D010134:Fenclonine / Q000494:pharmacology*; D009020:Morphine / Q000037:antagonists & inhibitors; D009619:Nociceptors / Q000187:drug effects; D010423:Pentazocine / Q000037:antagonists & inhibitors; D051381:Rats
D000700:Analgesics; D000701:Analgesics, Opioid; D000893:Anti-Inflammatory Agents; D009020:Morphine; D006916:5-Hydroxytryptophan; D001241:Aspirin; D010134:Fenclonine; D010423:Pentazocine; D003002:Clonixin