Asunto(s)
Aminoácidos Diaminos/farmacología , Encéfalo/metabolismo , AMP Cíclico/metabolismo , Antagonistas de Aminoácidos Excitadores , Adenosina/metabolismo , Aminoácidos/metabolismo , Animales , Glutamatos/farmacología , Cobayas , Técnicas In Vitro , Masculino , Receptores de Droga/efectos de los fármacosRESUMEN
After oral administration of bromazepam, 50 mg/kg/day for 14-28 days to rats, the rate of elimination of the unchanged drug from the blood increased by 20-40%, as determined from the half-lives of the blood decay curves during the first 4 hr after administration of an oral or intravenous test dose of bromazepam. During the chronic administration, the liver weight increased 30-40%, with concomitant enlargement of the liver. The hepatomegaly was associated with elevation of microsomal drug-metabolizing enzyme activities, including that responsible for the oxidation of bromazepam itself. Spectral characteristics of the isolated microsomes indicated that the manner by which bromazepam caused the elevation (induction) of the enzyme activities was of the "phenobarbital type" rather than the "methylcholanthrene type." Since certain steps of bromazepam metabolism take place in the liver, it appears reasonable to assume that the increase in the elimination rate found after chronic administration may depend upon the enhanced drug-metabolizing activities in the liver. The hepatomegaly and the associated elevation of enzyme activities returned to the normal states within 7 days after withdrawal of the drug. Neither the increase in the elimination rate nor the enzyme induction was observed with doses lower than 5 mg/kg.
Asunto(s)
Ansiolíticos/farmacología , Bromazepam/farmacología , Microsomas Hepáticos/enzimología , Aminopirina N-Demetilasa/metabolismo , Anilina Hidroxilasa/metabolismo , Animales , Bromazepam/administración & dosificación , Bromazepam/sangre , Inducción Enzimática/efectos de los fármacos , Femenino , Semivida , Cinética , Hígado/efectos de los fármacos , Masculino , Microsomas Hepáticos/efectos de los fármacos , Oxigenasas de Función Mixta/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Ratas , Estimulación QuímicaRESUMEN
Vesicles from guinea pig cerebral cortex prepared by homogenization in Krebs-Ringer buffer contained adenylate cyclase activity which was stimulated by the acidic amino acids, cysteine sulfinic and glutamic acids, and by norepinephrine as well as by an alkaloid, veratridine. With these vesicular preparations the concentrations of amino acids required for half-maximal stimulation were about 30 muM, only about 1/30 those necessary with intact-cell preparations. Nearly additive effects were observed when either of the active amino acids was combined with norepinephrine at their optimal concentrations.