title: Coadministration of tramadol and tizanidine in an experimental acute pain model in rat.
abstract: Preclinical Research The use of drug combinations to achieve a desired effect is a common practice in pharmacological reaserch and in clinical practice. The present study was designed to evaluate the potential synergistic antinociceptive interactions between tizanidine, an α-2-adrenoceptor agonist and tramadol on formalin-induced nociception in rat using isobolographic analyses. Tramadol (0.1-100 μg/paw) and tizanidine (0.01-10 μg/paw) were injected into the paw prior to formalin injection (1%). Both drugs produced a dose-dependent antinociceptive effect. The EC50 values were estimated for individual drugs, and isobolograms were constructed. Tizanidine (EC50  = 0.125 ± 0.026 μg) was more potent than tramadol (EC50  = 16.45 ± 6.4 μg). The combination of tramadol-tizanidine at fixed ratios of 1:1 (EC50exp  = 67.43 ± 11 μg; EC50teo  = 8.28 ± 3.2 μg) and 3:1 (EC50exp  = 31.25 ± 9.49 μg; CE50teo  = 12.36 ± 4.8 μg) generated subadditivity (antagonism). On the basis of the current preclinical data, the pharmacological profile of the combination of tramadol-tizanidine produced antagonism. Thus, the utmost caution is required during the use of this combination in clinical practice, due to their antagonistic interaction.
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, México, D.F., 11340, México.
authors.forename: Karla Lizet
authors.initials: KL
authors.lastname: Beltrán-Villalobos
authors.forename: Pamela Monserrat
authors.initials: PM
authors.lastname: Ramírez-Marín
authors.forename: Carlos Alberto Zúñiga
authors.initials: CA
authors.lastname: Cruz
authors.forename: Myrna
authors.initials: M
authors.lastname: Déciga-Campos
mesh_terms: D059787:Acute Pain / Q000188:drug therapy*; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D051381:Rats; D017208:Rats, Wistar; D014147:Tramadol / Q000008:administration & dosage*
chemical_list: D000700:Analgesics; D014147:Tramadol; C023754:tizanidine; D003000:Clonidine
keywords: antagonism; antinocception; nociception; tizanidine; tramadol