Analgesic efficacy of the combination metamizol+morphine after subchronic treatment in rats

Abstract

In the present study, the analgesic efficacy and the possible development of tolerance produced by the combination metamizol+morphine (562.3:5.6 mg/kg) during subchronic treatment (6 and 12 days) in arthritic rats using the PIFIR model was evaluated. This combination of metamizol+morphine produced the maximum analgesic efficacy (AUCE = 353.4 ± 24.7 au) when compared with morphine 5.6 mg/kg (AUCE = 196.6 ± 35.3 au), metamizol 562.3 mg/kg (AUCE = 262.8 ± 10.2 au), and morphine 10 mg/kg (AUCE = 316.6 ± 31.0 au) given in a single dose. The results were essentially the same when the combination was administered for 6 (AUCE = 325.4 ± 13.1 au) or 12 days (AUCE = 354.5 ± 9.6 au). In addition, the duration of the effect was longer when the combination metamizol+morphine was administered either in single or subchronic treatment. Development of tolerance to the analgesic effect was observed after 6 and 12 days of morphine administration. However, the analgesic effect produced by the metamizol+morphine combination remained constant (near 100%) during both subchronic treatments. The present data demonstrate that metamizol significantly attenuates the development of tolerance to morphine. The mechanism involved in this effect of metamizol remains to be determined. Drug Dev. Res. 51:260–267, 2000. © 2001 Wiley-Liss, Inc.