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Biomedical subjects

M Sandler

Publications and source records attributed to M Sandler.

At least 253 records · Page 14Linked to original sources
PubMed1978

Decreased urinary output of tyramine and its metabolites in depression.

Despite dramatic clinical improvement in about one-third of a group of severely depressed, medication-resistant patients one year after modified leucotomy, their relative decrease in conjugated and free tyramine output after an oral tyramine load remained unchanged and abnormal. Whilst a direct deficit in intestinal tyramine-conjugating ability still needs to be finally ruled out, this appears most compatible with a deficit due to bodily metabolic failure, perhaps a deficit in membrane transport which could be an essential aspect of the depressive illness syndrome. Attention is drawn to a similar defect in migraine. The two illnesses may represent a common predisposition which an appropriate triggering mechanism may transform to the florid disease. Biochemical detection of such vulnerability may have important diagnostic and predictive significance.

Administration, Oral↗
PubMed1978

Metabolism of 3, 4-dihydroxyphenylalanine, its metabolites and analogues in vivo in the rat: urinary excretion pattern.

The metabolism and interrelationships of orally and intraperitoneally administered L-dopa, related amino acids and their metabolites have been studied 2. Amino acids were decarboxylated. N-Methyldopa formed dopamine but not epinine. D-Dopa was absorbed from the intestine and metabolized by a series of reactions which resulted in greater decarboxylation than was observed after L-dopa. Transamination was a minor pathway. 3. m-Hydroxylated phenylpyruvic acids were poorly reduced, but vanilpyruvic acid was reduced fairly readily. Lactic acids were largely unchanged. Lactic and pyruvic acids formed phenylethylamines and their metabolites. Small amounts of phenylpyruvic acids may be decarboxylated to phenylacetic acids. 4. Glycine conjugates were formed from phenylacetic acids, a partially reversible change 3,4-Dihydroxyphenylacetic acid was metabolized to homovanillic and m-hydroxyphenylacetic acids, especially when given orally. Little 3-hydroxy-4-methoxyphenylacetic acid was oxidized to 3,4-dihydroxyphenylacetic acid but some increase in m-hydroxyphenylacetic acid excretion was observed. 5. 2-Phenylethanol analogues were largely converted to the corresponding acids. 3,4-Dihydroxyphenylethanol was partially m-O-methylated before oxidation. 6. beta-Phenylethylamine analogues were oxidized mainly to phenylacetic acids. but a variable amount of analogous phenylethanol was also formed, especially from m-tyramine. Dopamine was O-methylated, a process not readily reversible. It was also p-dehydroxylated following oral and intraperitoneal administration but not after oral neomycin; biliary excretion of amines may be involved in this sequence of events. N-Methylated amines were oxidized less readily than the parent amine. 7. Differences in route of administration resulted in quantitative changes in degradation pathways, an effect deriving, to some extent, from p-dehydroxylation and O-methylation in the gut.

Alcohols↗
PubMed1978

Cerebrovascular changes in migraine: secondary manifestations of a circulating humoral agent?

The cerebrovascular concomitants of migraine, initial vasoconstrictriction succeeded by vasodilatation, have long been considered the primary event in the pathogenesis of headache. In recent years, certain physicochemical concomitants of the attack have been identified, all involving blood platelets: these include hyperaggregability, decrease 5-hydroxytryptamine concentration and decreased monoamine oxidase activity. These changes may represent the response to a circulating humoral agent, deriving perhaps from the pulmonary vascular bed. The agent may not only bring about nonspecific damage of the kind described but be responsible for the cerebrovascular changes and stimulation of pain receptors characteristic of the disease. This circulating humoral agent may belong to the prostaglandin family.

Blood Platelets↗
PubMed1977

Deprenyl in Parkinson's disease.

In a double-blind crossover trial, (-)-deprenyl, a fast-acting selective monoamine-oxidase-B inhibitor without a "cheese effect", was given to 41 patients with idiopathic Parkinson's disease who were receiving maximum tolerated doses of levodopa either alone or combined with carbidopa ("Sinemet"). In a dose of 10 mg, daily or on alternate days, (-)-deprenyl prolonged the therapeutic effect of levodopa and was effective in mild "on-off" disabilities with end-of-dose akinesia; the majority of patients with nocturnal and early-morning akinesia also improved. No statistically significant improvement occurred in diurnal akinesia, and there was no improvement in patients with severe on-off disabilities with freezing and rapid oscillations ("yo-yo" effect). Levodopa-induced dyskinesias were aggravated in 14 patients. In 5 previously untreated patients, (-)-deprenyl alone gave no benefit, but when it was used with levodopa and carbidopa a mean dosage reduction of 200 mg levodopa daily was possible. Depression, present in 15 patients, was unchanged. (-)-Deprenyl in combination with smaller total daily doses of levodopa and a peripheral decarboxylase inhibitor may prove useful in reducing the frequency and severity of some types of on-off effect with overall benefit comparable to that obtained with larger doses of levodopa.

Adult↗
PubMed1977

Mass spectrometric and nuclear magnetic resonance confirmation of a 3,3-spirocyclic indole derivative formed from melatonin and related acyl tryptamines.

When melatonin is reacted with pentafluoropropionic anhydride for selected ion monitoring or electron capture gas chromatographic analysis a volatile product results. Examination of the product by combined gas chromatography mass spectrometry has established that the molecular weight of 360 corresponds to the addition of one molecule of pentafluoropropionic acid followed by dehydration. Further spectroscopic and chemical examination using mass spectrometry and nuclear magnetic resonance with isotopic labelling has established that the product is a 3,3-spirocyclic indole derivative. Several analogous compounds were also examined and their mass spectra studied.

Indoles↗
PubMed1976

Does phenylethylamine cause schizophrenia?

The model psychosis associated with amphetamine overdosage is known to bear a close resemblance to acute paranoid schizophrenia. Amphetamine is chemically similar to the endogenous sympathomimetic amine, phenylethylamine, which possess many of its pharmacological properties. It is suggested that some cases of schizophrenia may be associated with an abnormal phenylethylamine response, either from increased concentrations of the amine or from abnormal receptor sensitivity to it.

Brain↗
PubMed1976

In vivo assessment of decarboxylase inhibition or potentiation: urinary dopamine and L-dopa output after L-dopa administration.

In the L-Dopa treated rat, a decreased urinary output of free and conjugated dopamine and an increase in free and conjugated L-Dopa excretion after administration of decarboxylase-inhibiting drugs provide a good in vivo index of Dopa decarboxylase inhibition. With the exception of free dopamine output, which showed an equivocal change, these measurements appear to provide a good yardstick of decarboxylase status in man also. Using this approach, it was not possible to find any evidence of facilitation of decarboxylase action, in L-Dopa-treated parkinsonians given pyridoxine supplements, to account for the ability of this compound to neutralize the beneficial effect of L-Dopa.

Animals↗