RESUMEN
The optically active diastereometric erythro- and threo-3-thienyl-analogues 6a-d of 3-aryl-2-biphenylyl-3-hydroxy-propionic acids have been prepared. Some stereoisomers of 3-(3-thienyl)derivative 6b showed inhibition around 40% in the carrageenan-induced rat paw edema test.
Asunto(s)
Antiinflamatorios no Esteroideos/síntesis química , Lactatos/síntesis química , Tiofenos/síntesis química , Animales , Carragenina , Fenómenos Químicos , Química , Edema/inducido químicamente , Edema/prevención & control , Lactatos/farmacología , Espectroscopía de Resonancia Magnética , Masculino , Ratas , Ratas Endogámicas , Estereoisomerismo , Tiofenos/farmacologíaRESUMEN
The authors synthesized the title compounds as analogues of previously prepared potential antiphlogistic agents. Starting from appropriate carbonyl compound and alpha-metallated phenylacetic acid the diastereomeric racemate pairs were obtained; they were separated, attributed to erythro/threo-configuration by NMR and finally resolved. The potassium salts of the enantiomers were tested for analgesic and antiinflammatory activity, as well as for acute toxicity. Their action in the carrageenan test has been found to be stereoselective, but relatively poor or of briefly lastening.
Asunto(s)
Antiinflamatorios no Esteroideos/síntesis química , Analgésicos/síntesis química , Animales , Antiinflamatorios no Esteroideos/farmacología , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Conformación Molecular , Ratas , Ratas EndogámicasRESUMEN
The effects on central nervous system of a new low molecular weight heparin (OP/LMWH) were studied in mice and rats. The effect of OP/LMWH on respiration, blood pressure and heart rate was studied in guinea-pigs and rats. In these studies unfractionated heparin was used for comparison. OP/LMWH, up to 10 mg/kg/s.c., did not show any effect on central nervous system and did not increase the blood pressure, heart rate and respiration rate up to 10 mg/kg i.v. At the same dosages, heparin presented effects similar to those shown by OP/LMWH.
Asunto(s)
Heparina/farmacología , Analgésicos , Animales , Anticonvulsivantes , Presión Sanguínea/efectos de los fármacos , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Ratones , Peso Molecular , Oxotremorina/antagonistas & inhibidores , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Endogámicas , Reserpina/antagonistas & inhibidores , Respiración/efectos de los fármacos , Conducta Estereotipada/efectos de los fármacos , Yohimbina/antagonistas & inhibidoresRESUMEN
The aim of this study was to compare the antithrombotic and haemorrhagic effects of unfractionated heparin and OP/LMWH, a new low molecular weight heparin fragment, after subcutaneous administration in rats. Both heparins showed antithrombotic efficacy in a model of acute venous thrombosis even at 1 mg/kg; furthermore OP/LMWH presented a significantly higher activity in subacute venous thrombosis of the rat. At all the dosages tested OP/LMWH showed a significantly shorter bleeding time in the rat by the "transection" method, compared with unfractionated heparin. This study suggests the possibility of dissociating the antithrombotic and haemorrhagic effects of some heparin fractions.
