ISSN : 2146-3123
E-ISSN : 2146-3131

Non-opioid Analgesics and the Endocannabinoid System
Ruhan Deniz Topuz1, Özgur Gündüz1, Çetin Hakan Karadağ1, Ahmet Ulugöl1
1Department of Medical Pharmacology, Trakya University Faculty of Medicine, Edirne, Turkey
DOI : 10.4274/balkanmedj.galenos.2020.2020.6.66

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to produce antinociceptive effects mainly through peripheral COX-inhibition. Paracetamol and dipyrone are different from classical NSAIDs, because they exert weak anti-inflammatory activity; mechanisms other than peripheral COX inhibition appear to play role in their antinociceptive actions. In this review, we specified classical NSAIDs, paracetamol and dipyrone as "non-opioid analgesics" and discussed the mechanisms mediating participation of the endocannabinoid system in the antinociceptive effects of these analgesics. Non-opioid analgesics and their metabolites may activate cannabinoid receptors. In addition, several mechanisms are implicated in the elevation of endocannabinoid levels following administration of non-opioid analgesics. Of these, reduction of endocannabinoid degradation via FAAH and/or COX-2 inhibition, accumulation of arachidonic acid to endocannabinoid biosynthesis following COX inhibition, inhibition of cellular uptake of endocannabinoids directly or following inhibition of nitric oxide synthase production, and induction of endocannabinoid release are among the proposed mechanisms.

Keywords : endocannabinoids, dipyrone, NSAIDs, paracetamol
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