Topuz, Ruhan DenizGunduz, OzgurKaradag, Cetin HakanDokmeci, DikmenUlugol, Ahmet2024-06-122024-06-1220190008-42121205-7541https://doi.org/10.1139/cjpp-2019-0015https://hdl.handle.net/20.500.14551/20517The cannabinoid system has been suspected to play a role in the mechanisms of action of dipyrone and paracetamol. Our purpose was to measure the local endocannabinoid and N-acylethanolamide levels in the brain and spinal cord of rats following dipyrone and paracetamol administration. Nociception was assessed 1, 5, and 12 h following drug injections in Wistar rats, using tail-flick and hot-plate tests. The antinociceptive effects of dipyrone (150, 300, and 600 mg/kg, i.p.) and paracetamol (30, 100, and 300 mg/kg, i.p.) were observed. After administration of the highest doses of dipyrone and paracetamol, endocannabinoid (N-arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG)) and N-acylethanolamide (palmitoylethanolamide (PEA), oleoylethanolamide (OEA)) levels were measured in the periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and spinal cords of rats using tandem mass spectrometry with liquid chromatography. Increased 2-AG levels were observed in the PAG and the RVM 12 h after paracetamol injection; dipyrone exerted no action on 2-AG levels. Analgesic administrations led to a reduction in AEA levels in the RVM and spinal cord; similar decreases in PEA and OEA levels were observed in the RVM and the spinal cord. Dipyrone and paracetamol administrations appear to exert complicated effects on endocannabinoid and N-acylethanolamide levels in rats.en10.1139/cjpp-2019-0015info:eu-repo/semantics/closedAccessDipyroneEndocannabinoidN-AcylethanolamideParacetamolCannabinoid Cb1 ReceptorsInvolvementPainInflammationMetamizolBlockadeAgonistMetabolitesInhibitorsToleranceArticle971110351041Q3WOS:0004942616000042-s2.0-8507418460031283890Q3