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Biomedical subjects

A Gescher

Publications and source records attributed to A Gescher.

At least 127 records · Page 7Linked to original sources
PubMed1982

N-methylformamide: antitumour activity and metabolism in mice.

The antitumour activities of N-methylformamide, N-ethylformamide and formamide against a number of murine tumours in vivo (Sarcoma 180, M5076 ovarian sarcoma and TLX5 lymphoma) have been estimated. In all cases N-methyl-formamide had significant activity, formamide had marginal or no activity and N-ethylformamide had no significant activity. N-methylformamide and N-ethylformamide were equitoxic to the TLX5 lymphoma in vitro. Formamide was found as a metabolite in the plasma and urine of animals given N-methylformamide and N-ethylformamide, but excretion profiles do not support the hypothesis that formamide is an active antitumour species formed from N-alkylformamides. No appreciable metabolism of N-methylformamide occurred under a variety of conditions with liver preparations in vitro. N-methylformamide, but not N-ethylformamide or formamide, reduced liver soluble non-protein thiols by 59.8% 1 h after administration of an effective antitumour dose.

Animals↗
PubMed1982

Routes of elimination of hexamethylmelamine and pentamethylmelamine in the rat.

1. In the rat 40% of a dose of 25 mg/kg of hexamethylmelamine or pentamethylmelamine was excreted in the urine as metabolites, more than 95% of which were N2N4-dimethylmelamine and monomethylmelamine. 2. Biliary excretion of hexamethylmelamine or pentamethylmelamine and their N-demethylated metabolites accounted for less than 2% of the administered dose. Only 0 X 3% was excreted with the faeces, suggesting that there is intestinal reabsorption of a portion of the methylmelamines passing into the bile. 3. Conjugates of methylmelamines with glucuronic acid or sulphate were found only in minute quantities in the urine or bile of rats treated with hexamethylmelamine or pentamethylmelamine. However a conjugation product of pentamethylmelamine, of as yet unknown nature, is a major metabolite after pentamethylmelamine treatment.

Altretamine↗
PubMed1982

Studies of the pharmacology of N-methylformamide in mice.

When 400 mg/kg of 14C-methyl-labeled N-methylformamide (NMF) was injected ip into mice, the curve for plasma concentration of radioactivity versus time was superimposable on the curve obtained by measuring unmetabolized NMF with gas-liquid chromatography during the first 24 hrs. Radioactivity in plasma was measurable for 8 days after NMF administration, but NMF was not measurable by gas chromatography beyond 24 hrs after administration. Radioactivity was eliminated from the plasma after 60 hrs, with an apparent half-life of 71.1 hrs. Of the radioactivity injected with NMF, 73.6% was recovered in the urine in 24 hrs; 26.4% of this was unchanged NMF. Three percent of the administered radioactivity was exhaled as 14CO2 in 7 hrs at a constant rate of 0.007% per min. One urinary metablite was a stable precursor of formaldehyde, which decomposed to formaldehyde only after alkaline hydrolysis and may well be N-(hydroxymethyl)-formamide. The areas under the plasma concentration versus time curve were estimated after ip, iv, and oral administration of NMF. The bioavailability of NMF was 1.01 after oral administration and 1.10 after ip administration.

Administration, Oral↗
PubMed1978

Correlation of physicochemical properties with absorption and metabolism of some tricyclic drugs.

Octanol and dodecane partition coefficients, surface activity and adsorbability to activated charcoal were determined for six tricyclic psychotropic drugs with N-dimethylalkyl side chains. Surface activity correlated well with the partition coefficients, and all drugs obeyed the Langmuir adsorption isotherm. A correlation between the reciprocal of the death time of gold fish exposed to drugs and partition coefficients was observed. The extent to which the drugs were N-demethylated as measured by formaldehyde formed in rat liver homogenate incubations correlated with their adsorbability to activated charcoal but not with their ability to inhibit aniline-p-hydroxylase, nor was there a linear correspondence between N-DEMETHYLATION AND DRUG LIPOPHILICITY AS INDICATed by partition coefficients or surface activity.

Absorption↗
PubMed1976

Stereoselectivity of the distribution of labelled noradrenaline in rabbit aortic strips after inhibition of the noradrenaline-metabolizing enzymes.

Rabbit aortic strips (nerve-free, reserpine-pretreated or normal) whose noradrenaline-metabolizing enzymes were inhibited (by in vitro treatment with 0.5 mM pargyline for 30 min and by the presence of 0.1mM U-0521) were exposed to 1.18 muM labelled (-)- or (+)noradrenaline for 30 min. At the end of the incubation period some strips were used for analysis of radioactive (i.e., of noradrenaline and its metabolites), while for others the efflux of radioactivity was determined during 250 min of wash out with amine-free solution. An estimate of the original distribution of the amine into the various extraneuronal and neuronal compartments of the tissue was obtained by compartmental analysis of the efflux curves. 1. The mechanisms responsible for the accumulation of radioactivity in extraneuronal and axoplasmic compartments lack stereoselectivity; the rate constants for the efflux of radioactivity from these compartments are the same for (-)- and (+)noradrenaline. 2. The accumulation of radioactivity in storage vesicles is stereospecific with preference for the (-)isomer. 3. Despite the use of enzyme inhibitors, the "late neuronal efflux" of radioactivity (i.e., the efflux collected between the 200th and 250th min of wash out) contained a considerable proportion of metabolites of noradrenaline. The metabolism of noradrenaline was stereoselective: while dihydroxyphenylglycol (DOPEG) was the predominant metabolite in the efflux from strips incubated with (-)noradrenaline, a considerable part of the efflux from strips incubated with the (+) isomer consisted of dihydroxymandelic acid and "O-methylated and deaminated" metabolites (in addition to DOPEG).

Animals↗