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Biomedical subjects

M Sandler

Publications and source records attributed to M Sandler.

At least 325 records · Page 18Linked to original sources

m-Hydroxyphenylacetic acid formation from L-dopa in man: suppression by neomycin.

The increased excretion of m-hydroxyphenylacetic acid in the urine of patients with parkinsonism being treated with L-dopa was reduced by gut sterilization with neomycin. The p-de-hydroxylation step is thus brought about solely by the action of gut flora; the pathway is unlikely to be involved in the events within the brain leading to the therapeutic benefit effected by L-dopa.

Dihydroxyphenylalanine↗

Catecholamine and 5-hydroxyindole metabolism in immunosympathectomized rats.

1. The daily urinary excretion of normetadrenaline, metadrenaline, 4-hydroxy-3-methoxyphenylglycol, 4-hydroxy-3-methoxymandelic acid, dopamine, homovanillic acid, 5-hydroxytryptamine and 5-hydroxyindolylacetic acid has been estimated in the urine of immunosympathectomized and control rats.2. A method is given which allows separate spectrophotometric determination of 4-hydroxy-3-methoxyphenylglycol and 4-hydroxy-3-methoxymandelic acid in the same sample of rat urine. Metadrenaline and normetadrenaline were estimated by a modification of the method of Anton & Sayre (1966).3. Approximately 17% of the 4-hydroxy-3-methoxymandelic acid in rat urine is excreted in the free state, over 60% as a glucuronide conjugate and the remainder as a sulphate conjugate.4. Urinary excretion of 4-hydroxy-3-methoxyphenylglycol was approximately halved in immunosympathectomized rats (P<0.001). 4-Hydroxy-3-methoxymandelic acid output was significantly increased in treated animals (P<0.05) when expressed in terms of body weight. No significant difference was detected for any of the other compounds investigated.5. The results are discussed in the light of previous knowledge of the effect of immunosympathectomy on catecholamine metabolism.

Animals↗

The metabolism of orally administered L-Dopa in Parkinsonism.

1. Gas-liquid chromatographic methods were used to measure urinary acidic and alcoholic metabolites of L-DOPA, which had been administered in high oral dosage to patients with postencephalitic and idiopathic Parkinsonism.2. The output of these compounds was normal before treatment. During drug therapy, large quantities of the dopamine metabolites, homovanillic acid and dihydroxyphenylacetic acid, were excreted but traces only of 4-hydroxy-3-methoxyphenylethanol. Noradrenaline metabolites showed little change in output other than a small increase in 4-hydroxy-3-methoxymandelic acid.3. Information was obtained about a number of minor routes of degradation which might be implicated in the therapeutic action of L-DOPA. A raised output of m-hydroxyphenylacetic acid pointed to p-dehydroxylation of dihydroxyphenylacetic acid by gut flora. Evidence of transamination as a minor metabolic pathway was obtained by finding appreciable urinary levels of 4-hydroxy-3-methoxyphenyllactic acid. A keto-acid precursor of this compound may act as competitive inhibitor of an enzyme active in the normal degradation route of tyrosine, p-hydroxyphenylpyruvic acid oxidase, for increased amounts of p-hydroxyphenyllactic acid, the major metabolic derivative of p-hydroxyphenylpyruvic acid, accumulated in the urine during DOPA treatment.

Chromatography, Gas↗