Taber R I, Latranyi M B
Eur J Pharmacol. 1981 Nov 5;75(4):215-22. doi: 10.1016/0014-2999(81)90547-1.
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.
使用大鼠酵母足试验评估了对氯苯丙氨酸（PCPA）（一种血清素（5HT）生物合成抑制剂）拮抗三类镇痛药（阿片类激动剂（吗啡）、阿片类激动剂-拮抗剂（喷他佐辛）和非甾体抗炎药（阿司匹林和氯尼辛））的抗伤害感受作用的能力。在PCPA（300mg/kg腹腔注射）给药48小时后，这些药物等剂量的镇痛作用均被消除。PCPA（150mg/kg腹腔注射）使吗啡和阿司匹林的相对效价降低程度相同。该作用不能归因于痛觉过敏或与炎症机制的相互作用。PCPA并未改变氯尼辛的抗水肿活性，并且它阻断吗啡诱导的对未发炎足施加压力的反应时间增加，其程度与对发炎足相同。血清素前体5-羟色氨酸（5HTP，80mg/kg腹腔注射）恢复了所有四种药物的抗伤害感受活性。这些结果表明血清素可调节对具有不同作用机制的镇痛药的敏感性。
