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Biomedical subjects

T Horie

Publications and source records attributed to T Horie.

At least 523 records · Page 29Linked to original sources
PubMed1981

Studies on the metabolism of tripamide, a new antihypertensive agent. I. Characterization of metabolites in rats.

1. Tripamide (N-(4-aza-endo-tricyclo[5.2.1.0(2,6)]decan-4-yl)-4-chloro-3-sulphamoyl [carbonyl-14C]benzamide) was metabolized in rat to yield five metabolites which were separated by chromatography, and characterized by mass spectrometry and reverse isotope dilution analysis. 2. The five metabolites were identified as follows; N-(3(or 5)-hydroxy-4-aza-endo-tricyclo[5.2.1.0(2,6)]decan-4-yl)-4-chloro-3-sulphamoylbenzamide (3-hydroxy-tripamide); N-8(or 9)-hydroxy-4-aza-endo-tricyclo[5.2.1.0(2,6)]decan-4-yl)-4-chloro-3-sulphamoylbenzamide (8-hydroxy-tripamide); 4-chloro-3-sulphamoylbenzamide; 4-chloro-3-sulphamoylbenzoic acid; and 4-chloro-3-sulphamoylbenzoic acid-(N'-acetyl)hydrazide. 3. Tripamide was metabolized rapidly and the major metabolite was 4-chloro-3-sulphamoylbenzoic acid in rat blood. 4. After intravenous injection, the excretion rate of the hydroxylated tripamide into bile was about 2-3 times faster than that into urine.

Animals↗
PubMed1981

Studies of metabolism of tripamide, a new antihypertensive agent. II. Metabolism by the hepatic microsomal enzymes.

1. The metabolism of tripamide, N-(4-aza-endo-tricyclo[5.2.1.0(2.6)]decan-4-yl)-4-chloro-3-sulphamoylbenzamide, has been studied with rat liver microsomal preparations. 2. Hydrolysis of tripamide was induced by phenobarbitone pretreatment and inhibited by O-ethyl O-p-nitrophenyl phenylphosphonothioate (EPN), a classical inhibitor of hepatic microsomal arylamidase. The hydrolysis was also catalysed by partially purified rabbit liver microsomal arylamidase. 3. The hydroxylation of tripamide was induced by 3-methylcholanthrene and inhibited by CO. 4. Inhibition of the hydroxylation of tripamide by antibodies of cytochrome P-450 and P-448 was studied. The 8-hydroxylation was inhibited by both antibodies, but 3-hydroxylation was inhibited by neither.

Aminopeptidases↗
PubMed1979

Relationship of carcinogenicity, mutagenicity, and K-region reactivity in benz[c]acridines.

Benz[c]acridine and its 10 methyl-substituted derivatives were examined for chemical reactivity with osmium tetroxide and mutagenic activity on Salmonella typhimurium, and the results were contrasted with the electronic charge in the K region and the carcinogenic activity of benz[c]acridines. The addition of osmium tetroxide took place at the K region of benz[c]acridines. A linear relationship was established between the charge in the K region and the rate constant of the second-order reaction between osmium tetroxide and benz[c]acridines except the 5,7-dimethyl derivative whose substituent in the 5-position sterically hindered the reaction. Benz[c]acridines showed mutagenic activity in the presence of S-9 Mix, but not in the absence of S-9 Mix. There was a corresponding relationship among the K-region reactivity, mutagenic activity, and carcinogenic activity in benz[c]acridines. The only exception for this was the 7,11-dimethyl derivative in which the 11-methyl group had a steric effect on the ring-nitrogen atom. It was suggested that a common mechanism with regard to the reactivity of the K region is working in both carcinogenesis and mutagenesis. It was concluded that benz[c]acridines are activated, before they display a carcinogenic or mutagenic activity, to a proximate form such as 5,6-epoxides, through a metabolic process in which the nucleophilic property of the K region to react with electrophilic reagents plays an important role.

Acridines↗