INFLUENCE OF PIPERINE ON NIMESULIDE INDUCED ANTINOCICEPTION

Piperine (l-peperoyl piperidine), an alkaloid extracted from Piper nig rum Linn is an inhibitor of hepatic and other enzymes involved in the biotransformation of drugs. In the present study piperine showed a dos e dependent synergistic effect on nimesulide induced antinociception, in the acetic acid induced writhing test in mice. Piperine at a dose o f 10 mg/kg significantly (p < 0.001) increased the analgesic activity of nimesulide administered at a submaximal dose of 6.5 mg/kg, In the f ormalin test, nimesulide alone (10 mg/kg, oral) did not modify phase I or nociceptor mediated pain while a combination of nimesulide (10 mg/ kg) with piperine (10 mg/kg) significantly decreased it. In phase IT o r inflammatory pain, duration of formalin induced behaviour was 80 +/- 7 s, 61 +/- 7.3 s and 5.33 +/- 3.3 s in control, nimesulide treated a nd piperine plus nimesulide treated groups respectively, indicating a synergistic activity of piperine with nimesulide, The antinociceptive effect correlated well with increased plasma concentration of nimesuli de, The plasma concentration after oral administration of nimesulide ( 10 mg/kg) alone was 8.03 +/- 0.99 ug/mL. However, when it was administ ered with piperine (10 mg/kg), the plasma concentration of nimesulide increased to 11.9 +/- 0.23 ug/mL. This indicates that piperine inhibit s the biotransformation and metabolism of nimesulide leading to signif icantly (p < 0.05) higher levels of drug in the systemic circulation. The findings of the present study suggest that piperine could be used as a biological enhancer when coadministered with nimesulide, (C) 1998 John Wiley & Sons, Ltd.