RESUMO
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.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dipirona/sangue , Dipirona/farmacocinética , Morfina/farmacologia , Aminopirina/análogos & derivados , Aminopirina/sangue , Aminopirina/química , Ampirona/análogos & derivados , Ampirona/sangue , Ampirona/química , Animais , Calibragem , Cromatografia de Fase Reversa/métodos , Dipirona/análogos & derivados , Dipirona/química , Interações Medicamentosas , Masculino , Ratos , Ratos Wistar , Extração em Fase Sólida/métodosRESUMO
INTRODUCTION: Mirabilis jalapa Linn is a well-studied plant. The indigenous people of Mexico use Mirabilis jalapa to cure many infirmities including dysentery, diarrhea, muscular pain and abdominal colic. In the present investigation, we have further characterized some pharmacological properties of an extract of Mirabilis jalapa flowers; therefore, we intend to contribute to understand the pharmacological effects and clarify the complex use of this medicinal plant. RESULTS: The extract of Mirabilis jalapa (1-1000 mug/mL) exhibits an inhibitory effect (IC(50)=18+/-0.7 micorg/mL) on gut smooth muscle contractility whereas it stimulates the contraction of rabbit aortic muscle (EC(50)=11.60+/-0.26 micorg/mL) in a concentration-dependent manner. CONCLUSIONS: These effects were not due to either ACh or HIS receptors blockage, IP(3), cAMP, cGMP, Ca(2+) release from intracellular storage, or protein kinase mediated contraction-relaxation mechanisms. The effects inducted by the Mirabilis jalapa extract may involve a serotoninergic mechanism, which, in turn, interacts with other adrenergic systems. Further studies are necessary to identify the active compounds within the extract and to elucidate the mechanism of action.
Assuntos
Mirabilis , Parassimpatolíticos/farmacologia , Extratos Vegetais/farmacologia , Animais , Relação Dose-Resposta a Droga , Flores , Cobaias , Técnicas In Vitro , Masculino , Coelhos , Receptores de Serotonina/fisiologiaRESUMO
Acidity constants for the 5-amino-1,10-phenanthroline (5-Aphen) were determined in aqueous media, using SQUAD and SUPERQUAD programs. Spectrophotometry and potentiometry data were fitted to the best model to enable correlation of the following acidity equilibria: 5-AphenH = 5-Aphen + H+ (-log K = 5.78 +/= 0.03) and 5-AphenH2 = 5-AphenH2 = 5-Aphen + 2H+ (-log K = 6.89 +/= 0.07). UV absorptivity coefficients obtained suggest that the first protonation takes place on the nitrogens of the heterocycle ring and the second protonation could take place on the amino group. As expected, the electrochemical evidence of the 5-Aphen species depends on the degree of protonation.