D-propoxyphene and dipyrone co-administration produces greater antinociception and fewer adverse effects than single treatments in rats.

Author(s): Silva-Moreno A, Lopez-Munoz FJ, Cruz SL

Affiliation(s): Departamento de Farmacobiologia, Cinvestav, Sede Sur. Calzada de los Tenorios # 235, Col. Granjas Copa, Mexico D.F., 14330, Mexico.

Publication date & source: 2009-04-01, Eur J Pharmacol., 607(1-3):84-90. Epub 2009 Feb 14.

Publication type:

D-propoxyphene is a commonly prescribed opiate analgesic. Its use is limited by unwanted side effects at high doses and tolerance development after chronic administration. Dipyrone (also known as metamizol) is a non-steroidal anti-inflammatory drug extensively used in Latin America and Europe. The objective of this work was to evaluate the antinociceptive efficacy of a dipyrone/D-propoxyphene combination and the development of tolerance to its repeated administration in the tail flick test in rats. Male Wistar rats (200+/-20 g) were i.v. injected twice daily (8 h apart) with 0.31 mg/kg D-propoxyphene, 400 mg/kg dipyrone, or the combination of these drugs, at the same doses, until complete tolerance was observed. A time course of the effects for each administration was determined. At the doses tested, D-propoxyphene and dipyrone produced mild antinociception per se. Repeated administration resulted in complete tolerance to their antinociceptive effects by the sixth dose. The D-propoxyphene/dipyrone combination produced more antinociception than expected by the sum of individual drug effects. With this treatment, tolerance developed at the 15th administration. In animals already tolerant to D-propoxyphene or dipyrone alone, subsequent administration of the combination partially restored the antinociceptive effect. These results suggest that the use of this combination provides advantages over single drug therapies.