title: Tapentadol and nitric oxide synthase systems.
abstract: Tapentadol, a new analgesic drug with a dual mechanism of action (μ-opioid receptor agonism and norepinephrine reuptake inhibition), is indicated for the treatment of moderate to severe acute and chronic pain. In this paper, the possible additional involvement of the nitric oxide synthase (NOS) system in the antinociceptive activity of tapentadol was investigated using an unspecific inhibitor of NOS, L-NOArg, a relatively specific inhibitor of neuronal NOS, 7-NI, a relatively selective inhibitor of inducible NOS, L-NIL, and a potent inhibitor of endothelial NOS, L-NIO. Tapentadol (1-10 mg/kg, intraperitoneal) increased the threshold for mechanical (Randall-Selitto test) and thermal (tail-flick test) nociceptive stimuli in a dose-dependent manner. All four NOS inhibitors, administered intraperitoneally in the dose range 0.1-10 mg/kg, potentiated the analgesic action of tapentadol at a low dose of 2 mg/kg in both models of pain. We conclude that NOS systems participate in tapentadol analgesia.
authors.affiliation: aDepartment of Pharmacodynamics, Centre for Preclinical Research and Technology (CePT) bDepartment of Orthopaedics and Rehabilitation, 2nd Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bujalska-Zadrożny
authors.forename: Renata
authors.initials: R
authors.lastname: Wolińska
authors.forename: Emilia
authors.initials: E
authors.lastname: Gąsińska
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Nagraba
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017450:Receptors, Opioid, mu / Q000819:agonists; D000077432:Tapentadol
chemical_list: D000701:Analgesics, Opioid; D010636:Phenols; D017450:Receptors, Opioid, mu; D019001:Nitric Oxide Synthase; D000077432:Tapentadol