Beiträge zu Abbau und Ausscheidung von<i>N′</i>-[4-Methyl-benzolsulfonyl]-N′-butyl-harnstoff (D 860)

Wittenhagen, G; Mohnike, G; Langenbeck, Wolfgang

doi:10.1515/bchm2.1959.316.1.157

Cited by 27 publications

(7 citation statements)

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“…Tolbutamide may well block 5-HIAA efflux from the brain as it is metabolized to N-p-carboxybenzenesulphonyl N1 -n butylurea (Wittenhagen, Mohnike & Langenbock, 1959) which is structurally similar to probenecid (p-di-n-propylsulphamyl-benzoic acid).…”

Section: Discussionmentioning

confidence: 99%

Drugs Altering Insulin Secretion: Effects on Plasma and Brain Concentrations of Aromatic Amino Acids and on Brain 5‐hydroxytryptamine Turnover

Curzon

Fernando

1977

British J Pharmacology

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I An investigation was made into the effects of drugs which alter insulin secretion on the concentrations Of to hanWandacids in plasma and brain and on 5-hydroxv- streptozotocin, propranolol, tolbutamide and phentolamine. 2 Tolbutamide and phentolamine increased the plasma insulin concentrations by 100% and 300% respectively but with little effect on the brain/plasma ratios for the aromatic amino acids. Previously propranolol was found to decrease plasma insulin by 50% without altering the above ratios. The ratios were decreased by streptozotocin but only when plasma insulin fell by more than 50%. 3 Phentolamine and propranolol did not alter the brain/plasma ratios for the aromatic amino acids in streptozotocin-treated rats. 4 The results suggest that only large changes of insulin secretion e.g. those associated with food intake or aminophylline injection are likely to alter appreciably the brain/plasma ratios for the aromatic amino acids. STolbutamide displaced tryptophan from its binding to plasma albumin and increased brain 5-HIAA probably by inhibiting 5-HIAA efflux from brain. The other drugs did not alter brain 5-HT or 5-HIAA concentrations.

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Section: Discussionmentioning

confidence: 99%

Drugs Altering Insulin Secretion: Effects on Plasma and Brain Concentrations of Aromatic Amino Acids and on Brain 5‐hydroxytryptamine Turnover

Curzon

Fernando

1977

British J Pharmacology

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“…The urinary excretion product of tolbutamide (D 860-COOH) in man, has a carboxyl group substituted for a methyl group in the molecule and lacks blood sugar lowering properties [24]. The main excretion product of HB 419, which is a 4-hydroxy-cyclohexyl derivative (HB 419-0H) of the original substance, has a capacity for lowering the blood sugar that is consistently weaker than that of the original substance [13].…”

Section: Methodsmentioning

confidence: 99%

Action of some hypoglycaemic sulphonylureas on the oxygen consumption of isolated pancreatic islets of mice

Stork

Schmidt²,

Westman³

et al. 1969

Diabetologia

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“…The major route of sulofenur metabolism is through benzylic hydroxylation of the indanesulfonyl moiety, and the major metabolites in all species studied are LY264912 and LY227938 (XII and XIII, respectively, in Table II) (10). In many respects its metabolism is thus similar to that of tolbutamide (11,12) and other sulfonylureas having a toluenesulfonyl group (13,14). The dog apparently lacks the ability to carry out this hydroxylation, however, resulting in a much longer half-life for sulfonylureas such as tolbutamide in this species (11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 95%

Comparison of metabolism and toxicity to the structure of the anticancer agent sulofenur and related sulfonylureas

Ehlhardt¹,

Woodland²,

Worzalla³

et al. 1992

Chem. Res. Toxicol.

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The metabolic formation of p-chloroaniline from the oncolytic agent sulofenur [N-(5-indanesulfonyl)-N'-(4-chlorophenyl)urea, LY186641,] and from similar diaryl-substituted sulfonylureas, and its possible relevance to the compound's toxicity, was studied. In previous studies it was found that significant amounts of metabolites such as 2-amino-5-chlorophenyl sulfate (II), which is also a metabolite of p-chloroaniline, are formed from sulofenur in mice, rats, monkeys, and humans. The metabolism of N-(4-tolyl)-N'-(2-hydroxy-4-chlorophenyl)-urea (V) was studied, and V was not found to be an intermediate in the metabolic formation of II from the sulfonylurea N-(4-tolyl)-N'-(4-chlorophenyl)urea (LY181984, III). The amounts of this p-chloroaniline metabolite (II) formed in C3H mice from a series of diarylsulfonylureas were found to correlate with the compound's propensities to form methemoglobin, one notable toxicity of p-chloroaniline. This metabolism was also found to correlate with the structure of the arylsulfonyl moiety of the sulfonylurea. Other evidence supports the hypothesis that p-chloroaniline is directly formed by metabolism of sulfofenur and similar diarylsulfonylureas as well. Metabolic formation of p-chloroaniline thus appears to be a plausible explanation for the methemoglobinemia and anemia found to be dose-limiting toxicities of sulofenur in Phase I trials.

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Beiträge zu Abbau und Ausscheidung vonN′-[4-Methyl-benzolsulfonyl]-N′-butyl-harnstoff (D 860)

Cited by 27 publications

References 0 publications

Drugs Altering Insulin Secretion: Effects on Plasma and Brain Concentrations of Aromatic Amino Acids and on Brain 5‐hydroxytryptamine Turnover

Drugs Altering Insulin Secretion: Effects on Plasma and Brain Concentrations of Aromatic Amino Acids and on Brain 5‐hydroxytryptamine Turnover

Action of some hypoglycaemic sulphonylureas on the oxygen consumption of isolated pancreatic islets of mice

Comparison of metabolism and toxicity to the structure of the anticancer agent sulofenur and related sulfonylureas

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