title: Synergistic interaction between tapentadol and flupirtine in the rat orafacial formalin test.
abstract: Combination therapy with two or more analgesics is widely used for conditions associated with moderate to severe pain. Combinations of diverse analgesics with different modes of action can improve the risk-benefit ratio of analgesic treatments. The aim of this study is to evaluate the antinociceptive effect of tapentadol (TAP) and flupirtine (FLP), when administered separately or in combination, as well as their synergistic interaction in the orofacial formalin test in rats. After i.p. injection of TAP at different doses (2, 5, 10 and 15mg/kg), the biphasic nociceptive behavior was reduced in a dose-dependent manner in both phase I and II. Conversely, i.p. injection of FLP at different doses (0.6, 1.6, 3.3, 6.6, 16.6 and 22.2mg/kg) induced a dose-dependent antinociceptive effect in phase II only. TAP was found to be more effective than FLP. The interaction between TAP and FLP was synergistic in phase II with an interaction index (γ) of 0.50±0.24. The data reported in this study indicate that FLP enhances the antinociceptive effect of TAP and this drug combination might be potentially useful in the treatment of chronic pain.
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon 305-764, South Korea.
authors.forename: Hongki
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Veterinary Medicine, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: De Vito
authors.affiliation: Department of Veterinary Sciences, University of Pisa, Via Livornese (lato monte) 1, San Piero a Grado, 56122 Pisa, Italy. Electronic address: mario.giorgi@vet.unipi.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Giorgi
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon 305-764, South Korea. Electronic address: hiyun@cnu.ac.kr.
authors.forename: Hyoin
authors.initials: H
authors.lastname: Yun
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005157:Facial Pain / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D005557:Formaldehyde / Q000494:pharmacology*; D008297:Male; D059225:Nociception / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D000077432:Tapentadol
chemical_list: D000631:Aminopyridines; D000700:Analgesics; D010636:Phenols; D005557:Formaldehyde; D000077432:Tapentadol; C034161:flupirtine
keywords: Drug interaction; Flupirtine; Orofacial formalin test; Pharmacodynamics; Rat; Tapentadol