title: Metamizol potentiates morphine antinociception but not constipation after chronic treatment.
abstract: This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.
authors.affiliation: Departamento de Farmacobiología, CINVESTAV-IPN, Calz. de los Tenorios No. 235 Col. Granjas Coapa, Deleg. Tlalpan, C.P. 14330, Mexico City, Mexico.
authors.forename: Gloria P
authors.initials: GP
authors.lastname: Hernández-Delgadillo
authors.forename: Rosa
authors.initials: R
authors.lastname: Ventura Martínez
authors.forename: Ma Irene
authors.initials: MI
authors.lastname: Díaz Reval
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Domínguez Ramírez
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Muñoz
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D003248:Constipation / Q000139:chemically induced*; D004177:Dipyrone / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D009270:Naloxone; D004177:Dipyrone; D009020:Morphine