RESUMEN

In order to evaluate the pharmacokinetics of metamizol in the presence of morphine in arthritic rats, after subcutaneous administration of the drugs, an easy, rapid, sensitive and selective analytical method was proposed and validated. The four main metamizol metabolites (4-methylaminoantipyrine, 4-aminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoantipyrine) were extracted from plasma samples (50-100µl) by a single solid-phase extraction method prior to reverse-phase high performance liquid chromatography with diode-array detection. Standard calibration graphs for all metabolites were linear within a range of 1-100µg/ml (r(2)≥0.99). The intra-day coefficients of variation (CV) were in the range of 1.3-8.4% and the inter-day CV ranged from 1.5 to 8.4%. The intra-day assay accuracy was in the range of 0.6-9.6% and the inter-day assay accuracy ranged from 0.9 to 7.5% of relative error. The lower limit of quantification was 1µg/ml for all metabolites using a plasma sample of 100µl. Plasma samples were stable at least for 4 weeks at -20°C. This method was found to be suitable for studying metamizol metabolites pharmacokinetics in arthritic rats, after simultaneous administration of metamizol and morphine, in single dose.

Asunto(s)

RESUMEN

This paper describes the synthesis of new cyclic imides obtained by reaction with aminophenazone (CAS 58-15-1, 4-aminoantipyrine) and different anhydrides with further cyclization with acetic acid under reflux. Their structures were confirmed by spectral data (IR and NMR) and elemental analysis. The analgesic activity of the synthesized compounds was investigated initially with the writhing test in mice and the most promising compound, a 3,4-dichloromaleimide derivative (3), was analyzed using other models of nociception. The results indicated that compound 3 exerts potent analgesic activity in mice, being more active than some reference drugs. The analgesia caused by this compound was not reversed by naloxone in the writhing test. In the hotplate test, compound 3 did not increase the latency period of pain induced by thermal stimuli, confirming that it does not interact with opioid systems.

Asunto(s)

Asunto(s)

RESUMEN

A case of acute, transient agranulocytosis and thrombocytopenia associated with ingestion of dipyrone is reported. This once widely used analgesic, which is now banned in the United States, was obtained by the patient as "aspirin" while traveling in Mexico. Studies of the effects of this patient's serum on purified CD34+ marrow cells, which were highly enriched for hematopoietic progenitors, showed not only a drug-dependent suppression of the in vitro growth of myeloid progenitors, as has been reported previously, but also a drug-dependent suppression of primitive multipotential progenitors (CFU-Mix) and erythroid progenitors (BFU-E). These findings indicate that autoimmune, antibody-hapten interactions which have been reported to occur in dipyrone- and aminopyrine-induced agranulocytosis are not restricted to the neutrophil lineage.

Asunto(s)

RESUMEN

Rat macrophage monolayers pre-treated with endotoxin release into the incubating fluid a factor (MW greater than 10,000) capable of inducing writhing in mice (MNF). This release was inhibited by dipyrone (3.5-35 micrograms/ml) but not by indomethacin (0.5-2 micrograms/ml). Writhing in mice induced by the factor is blocked by dipyrone (0.5-50 mg/kg) and indomethacin (0.5-2 mg/kg). These results indicate that in addition to the previously described direct blockade of hyperalgesia by dipyrone, this drug may also affect the release of MNF, which induces in vivo nociception through the release of prostaglandin-like substances.

Asunto(s)

RESUMEN

Eighteen of nineteen patients reported relief from chronic pain (40 to 100%, analogue scale) lasting from a few hours to up to two months after single or repeated regional infusion of dipyrone into a limb. A tendency towards increased duration of pain relief was observed after repeated infusions. The present series of observations in man and experiments with rat paw hyperalgesia are consistent with the interpretation that dipyrone blocks a persistent hyperalgesic state which may result from a previous frequent nociceptive stimulation (memory?) rather than an ongoing inflammatory process.

Asunto(s)

Asunto(s)

RESUMEN

Previous studies have shown that phenylbutazone, another pyrazolone, inhibits thyroid peroxidase activity and interferes with iodide organification. We have developed "in vitro" studies with rat particulated peroxidase and lactoperoxidase (LPO) to study the effects of dipyrone upon thyroid peroxidase and to determine the type of inhibition. The 3-monoiodothyrosine (MIT) and 3,5-diiodothyrosine (DIT) synthesis was markedly affected by 6 X 10(-4) M dipyrone with inhibitions of 59% and 30% respectively. No difference was observed with lower concentrations. Inhibition of peroxidase activity (Triiodide assay) was found when crude rat peroxidase preparations and LPO were incubated with dipyrone in concentrations ranging from 10(-3) M to 10(-8) M, with a Ki of 2.5 X 10(-5) M and 4 X 10(-5) M respectively. Guaiacol peroxidation was scarcely affected by the action of the drug; 10(-3) M produced inhibition of 50%. Line weaver-Burk: plots were used to investigate the inhibition of LPO activity by dipyrone. The inhibition by the drug was competitive with the iodide. We may conclude that dipyrone and other drugs of the pyrazolone group act upon peroxidase activity "in vitro", by an inhibition of competitive type and in presence of iodide.

Asunto(s)

Asunto(s)

RESUMEN

Female pregnant rats of 2BAW strain were divided in 2 groups: the 1st, received 50 mg/kg corporal weight of sodium 1-phenyl-2,3-dimethyl-5-pyrazolon-4-methylamino-methane sulfonate (Dipyrone), single dose daily, by i.p. injections, from 16th to 20th day of pregnancy; the 2nd, received 0,5 ml of distilled water, single dose daily, by i.p. injections, during the same period. All the animals were sacrificed 2 hours after the last injection. The biochemical results of nucleic acids in the placentas and fetal livers, and the caryometric data of trophoblastic giant cells and fetal hepatocytes, demonstrated that: 1. When compared the 2 groups, as much the nucleic acids levels (RNA and DNA) of placentas as the nuclear size of trophoblastic giant cells, do not presented statistical differences; 2. The biochemical levels of nucleic acids (RNA and DNA) of fetal livers decreased, while the nuclear size of hepatocytes increased in the experimental group, with reference to control group.

Asunto(s)

Asunto(s)