Tizanidine Increases Antinociceptive Effect and Prevents Gastric Damage Induced by Ketorolac in the Rat
Version of Record online: 21 NOV 2012
© 2012 Wiley Periodicals, Inc.
Drug Development Research
Volume 74, Issue 1, pages 38–42, February 2013
How to Cite
Rodríguez-Silverio, J., Sánchez-Mendoza, M. E., Arrieta-Valencia, J., Rocha-Gonzalez, H. I. and Flores-Murrieta, F. J. (2013), Tizanidine Increases Antinociceptive Effect and Prevents Gastric Damage Induced by Ketorolac in the Rat. Drug Dev. Res., 74: 38–42. doi: 10.1002/ddr.21054
- Issue online: 27 FEB 2013
- Version of Record online: 21 NOV 2012
- Manuscript Accepted: 21 OCT 2012
- Manuscript Received: 16 OCT 2012
- Instituto Politécnico Nacional
- Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas
- isobolographic analysis;
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID) effective in the treatment of moderate to severe pain. Tizanidine, an α-2-adrenoceptor agonist with myospasmolytic action, is indicated for the treatment of back pain either as monotherapy or in combination with NSAIDs. However, side effects may limit their use. As both drugs produce side effects that are dose dependent, a combination of these drugs appears in order to reduce the dose required for efficacy and, consequently, side effects. In this study, we evaluated the potential synergistic effect of these drugs in the thermal paw stimulation model and their effect on gastric ulcer production in response in the rat. Dose-response curves for ketorolac and tizanidine were constructed and from these, an ED40 value was obtained. Isobolographic analysis was carried out based on 0.5:0.5 proportions. In addition, protective effect of tizanidine against ketorolac-induced gastric damage was evaluated. A synergistic interaction in thermal hyperalgesia and gastroprotective activity was observed, suggesting a good therapeutic potential of this combination in the treatment of pain.