Department of Medical Pharmacology, Trakya University School of Medicine, Edirne, Turkey
Balkan Med J. 2020 Oct 23;37(6):309-315. doi: 10.4274/balkanmedj.galenos.2020.2020.6.66. Epub 2020 Jun 19.
Non-steroidal anti-inflammatory drugs produce antinociceptive effects mainly through peripheral cyclooxygenase inhibition. In opposition to the classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone exert weak anti-inflammatory activity, their antinociceptive effects appearing to be mostly due to mechanisms other than peripheral cyclooxygenase inhibition. In this review, we classify classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone as “non-opioid analgesics” and discuss the mechanisms mediating participation of the endocannabinoid system in their antinociceptive effects. Non-opioid analgesics and their metabolites may activate cannabinoid receptors, as well as elevate endocannabinoid levels through different mechanisms: reduction of endocannabinoid degradation via fatty acid amide hydrolase and/or cyclooxygenase-2 inhibition, mobilization of arachidonic acid for the biosynthesis of endocannabinoids due to cyclooxygenase inhibition, inhibition of endocannabinoid cellular uptake directly or through the inhibition of nitric oxide synthase production, and induction of endocannabinoid release.
非甾体抗炎药主要通过抑制外周环氧化酶产生镇痛作用。与经典的非甾体抗炎药相反，对乙酰氨基酚和安乃近的抗炎活性较弱，其镇痛作用似乎主要不是通过抑制外周环氧化酶来实现的。在这篇综述中，我们将经典的非甾体抗炎药、对乙酰氨基酚和安乃近归类为“非阿片类镇痛药”，并讨论了内源性大麻素系统参与其镇痛作用的机制。非阿片类镇痛药及其代谢物可能通过不同的机制激活大麻素受体，并升高内源性大麻素水平：通过抑制脂肪酸酰胺水解酶和/或环氧化酶-2 来减少内源性大麻素的降解，由于环氧化酶抑制，动员花生四烯酸用于内源性大麻素的生物合成，直接或通过抑制一氧化氮合酶的产生来抑制内源性大麻素的细胞摄取，以及诱导内源性大麻素的释放。
