RESUMO
The anticonvulsive effects of 5-allyl-(beta-hydroxy)propyl-N-phenylbarbituric acid (AP) and the product of its tissue and extraneous metabolism, alpha-allyl-alpha-allophanyl-gamma-butyrolactone (T1), were compared with the effect of phenobarbital. The anticonvulsive action of the substituted butyrolactone was more potent but shorter than that of AP, and the drug showed no hypnotic or general anesthetic action. The effect of AP was similar but much more prolonged.
Assuntos
4-Butirolactona/farmacologia , Anticonvulsivantes , Barbitúricos/farmacologia , Furanos/farmacologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/toxicidade , Animais , Barbitúricos/análogos & derivados , Barbitúricos/toxicidade , Convulsivantes , Eletrochoque , Dose Letal Mediana , Masculino , Camundongos , Fenobarbital/farmacologia , Convulsões/fisiopatologiaRESUMO
Simulataneous oral administration of butylhydroxytoluene (BHT) (50 or 100 mg/kg) with indomethacin (IND) (3, 6 or 20 mg/kg) prevented the damaging effect of IND on the rat gastric mucosa. Butylhydroxyanisole (BHA) and nordihydroguiaretic acid (NDGA) rather potentiated than prevented the noxious action of IND. A reduction of IND toxicity without affecting its anti-inflammatory action seems to be possible to achieve by concomitant administration of IND with BHT.
Assuntos
Antioxidantes/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Indometacina/toxicidade , Administração Oral , Animais , Antioxidantes/administração & dosagem , Hidroxianisol Butilado/farmacologia , Hidroxitolueno Butilado/farmacologia , Catecóis/farmacologia , Interações Medicamentosas , Indometacina/administração & dosagem , Masculino , Masoprocol , RatosRESUMO
Nordihydroguaiaretic acid inhibits prostaglandin (PG) biosynthesis in vitro (ID50=228 muM), with a slope of dose-response curve high (b=209) as compared with indomethacin (ID50=0.1 muM, b=72.1). Butylated hydroxyanisole, in contrast to inactive butylated hydroxytoluene, inhibits PG biosynthesis (ID50=107 muM, b=63). Only norihydroguaiaretic acid (100 mug, s.p.) inhibited the postcarrageenin edema of rat paw. Butylated hydroxyanisole (10 mug, s.p.) given together with a subthreshold (1 mug) dose of indomethacin inhibited the paw edema by 35%, while butylated hydroxytoluene and nordihydroguaiaretic acid produced a similar effect only when given at 10-fold higher doses. The results suggest the possibility of potentiation and prolongation of the anti-inflammatory effect of indomethacin by its simultaneous administration with an antioxidant, butylated hydroxyanisole.