RESUMO
2-(2-Isopropyl-5-indanyl)propionic acid (UP 517-03) is a new anti-inflammatory agent with marked analgesic and antipyretic properties. The anti-inflammatory potency is greater than that of phenylbutazone but lower than that of indometacin. This effect is observed also in adrenalectomized rats. The analgesic activity in the Randall and Selitto test is equipotent to that of indometacin, but this potency is lower in the other tests. In lowering brewer's yeast-induced fever in rats, UP 517-03 is as potent as indometacin and 10 times more effective than phenylbutazone. Considering from pharmacological index, UP 517-03 is tolerated as well as phenylbutazone and better than indometacin.
Assuntos
Anti-Inflamatórios/farmacologia , Propionatos/farmacologia , Analgésicos , Animais , Anti-Inflamatórios não Esteroides , Comportamento Animal/efeitos dos fármacos , Coagulação Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Sistema Digestório/efeitos dos fármacos , Cães , Feminino , Cobaias , Hemodinâmica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Masculino , Camundongos , Ratos , Respiração/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamenteRESUMO
The antipyretic effect of UP 517-03 was studied in rabbits, provided with a cannula in the lateral cerebral ventricle. Given orally as a curative treatment, UP 517-03 can abolish hyperthermic reactions induced by intracerebroventricular injection of sodium arachidonate or bacterial endotoxin. A comparison with acetylsalicylic acid and indomethacin is given. UP 517-03 does not modify the temperature of normothermic rabbits. These results suggests that the antipyretic action of UP 517-03 can be explained by an effect of this substance on the metabolism of arachidonic acid in brain.
Assuntos
Anti-Inflamatórios não Esteroides , Indanos/farmacologia , Indenos/farmacologia , Propionatos/farmacologia , Animais , Ácidos Araquidônicos/antagonistas & inibidores , Aspirina/farmacologia , Temperatura Corporal/efeitos dos fármacos , Endotoxinas/antagonistas & inibidores , Indometacina/farmacologia , Masculino , Coelhos , SalmonellaRESUMO
Various 2-alkyl-alpha-methyl- and 2-alkylindan-5-acetic acids have been prepared. The acids, which can exist in two diastereoisomeric forms that cannot be separated by crystallization or chromatography, can be analyzed in their mixture by NMR in the presence of Eu(dpm)3. It has been possible to reconstitute the two pure racemic 2-isopropyl-alpha-methylindan-5-acetic acids from their enantiomers obtained after resolution of the mixtures through salts with various active bases. The relative configuration of the two asymmetric centers of one of the diastereoisomers salts with various active bases. The relative configuration of the two asymmetric centers of one of the diastereoisomers has been determined by X-ray crystallography. The absolute configurations of the resolved acids have been established by a comparative study of their CD curves. The antiinflammatory and analgesic properties of these compounds as functions of their structure and stereochemistry are discussed.
