Pini L A, Vitale G, Ottani A, Sandrini M
Department of Internal Medicine, Clinical Pharmacology Unit, University of Modena, Italy.
J Pharmacol Exp Ther. 1997 Feb;280(2):934-40.
Paracetamol at the dose of 400 mg/kg i.p. displayed antinociceptive activity in the hot-plate test and the formalin test. Moreover, it induced a significant increase in brain serotonin (5-HT) concentration and a reduction in the number of 5-HT2 receptors in cortical membranes. Pretreatment with naloxone abolished this antinociceptive activity both in the hot-plate test and in the first phase of the formalin test without affecting the serum concentration of paracetamol. At the same time, naloxone prevented the increase in 5-HT concentration in the central nervous system and the reduction in 5-HT2 receptors in cortical membranes. Competition experiments demonstrated that paracetamol possesses affinity for [3H]naloxone binding sites. The action of morphine on nociception and on the serotonergic system was similar to that of paracetamol; all morphine-induced effects were blocked by naloxone. These data provide further evidence for a central antinociceptive effect of paracetamol and support the hypothesis that paracetamol exerts its antinociceptive activity through the serotonergic system. Moreover, our results point to the relationship between serotonergic and opiatergic systems in the antinociceptive activity of paracetamol.
腹腔注射剂量为400mg/kg的对乙酰氨基酚在热板试验和福尔马林试验中显示出抗伤害感受活性。此外，它还能使脑血清素（5-羟色胺，5-HT）浓度显著升高，并使皮质膜中5-HT2受体数量减少。用纳洛酮预处理可消除热板试验和福尔马林试验第一阶段的这种抗伤害感受活性，且不影响血清中对乙酰氨基酚的浓度。同时，纳洛酮可阻止中枢神经系统中5-HT浓度的升高以及皮质膜中5-HT2受体数量的减少。竞争实验表明，对乙酰氨基酚对[3H]纳洛酮结合位点具有亲和力。吗啡对伤害感受和血清素能系统的作用与对乙酰氨基酚相似；所有吗啡诱导的效应均被纳洛酮阻断。这些数据为对乙酰氨基酚的中枢抗伤害感受作用提供了进一步证据，并支持了对乙酰氨基酚通过血清素能系统发挥其抗伤害感受活性的假说。此外，我们的结果表明血清素能系统与阿片肽能系统在对乙酰氨基酚的抗伤害感受活性中存在关联。
