title: Antinociceptive effects of tramadol in co-administration with  metamizol after single and repeated administrations in rats.
abstract: Combinations of two analgesic drugs of the same or different class are widely used in clinical therapy to enhance its antinociceptive effects and reduce the side effects. In order to evaluate a possible antinociceptive synergistic interaction of metamizol s.c., a nonsteroidal antiinflammatory drug (NSAID), and tramadol s.c., an atypical opioid (opioid receptor agonist), were administered alone or in combination. In the present study, the antinociceptive efficacy and the possible development of pharmacological tolerance produced by the combination tramadol plus metamizol during a 4-day treatment in rats using the plantar test was evaluated. Male Wistar rats were s.c. injected with tramadol (17.8 mg/kg), metamizol (177.8 mg/kg) or the combination tramadol plus metamizol three times a day for 4 days. Both metamizol and tramadol produced antinociceptive effects with a low rate trend towards tolerance development at the end of the treatment. The antinociceptive efficacy of tramadol and metamizol co-administration gradually decreased after the second injection. These data suggest that when the combination is given in a unique administration it results in an important potentiation of their individual antinociceptive effects. But, the repeated coadministration of tramadol plus metamizol results in a development of tolerance.
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y Estudios Avanzados, Sede Sur, Calzada de los Tenorios 235, Colonia Granjas Coapa, México, DF, CP 14330, México.
authors.forename: Luis Alfonso
authors.initials: LA
authors.lastname: Moreno-Rocha
authors.forename: Adriana Miriam
authors.initials: AM
authors.lastname: Domínguez-Ramírez
authors.forename: Alma Rosa
authors.initials: AR
authors.lastname: Cortés-Arroyo
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Bravo
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: López-Muñoz
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D004177:Dipyrone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D008297:Male; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D014147:Tramadol / Q000008:administration & dosage*
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014147:Tramadol; D004177:Dipyrone