title: D-propoxyphene and dipyrone co-administration produces greater antinociception and fewer adverse effects than single treatments in rats.
abstract: 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.
authors.affiliation: Departamento de Farmacobiología, Cinvestav, Sede Sur. Calzada de los Tenorios # 235, Col. Granjas Copa, México D.F., 14330, Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Silva-Moreno
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Muñoz
authors.forename: Silvia L
authors.initials: SL
authors.lastname: Cruz
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011431:Dextropropoxyphene / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004177:Dipyrone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D007275:Injections, Intravenous; D008297:Male; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004177:Dipyrone; D011431:Dextropropoxyphene