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M B Youdim

Publications and source records attributed to M B Youdim.

At least 271 records · Page 15Linked to original sources

The metabolism of 5-hydroxytryptamine and beta-phenylethylamine in perfused rat lung and in vitro.

1 Metabolism of 5-hydroxytryptamine (5-HT) and beta-phenylethylamine (PHE) by monoamine oxidase (MAO) was investigated in rat isolated lungs and in mitochondrial preparations from rat lung. 2. In perfused lungs 5-HT metabolism had an apparent Km of 2 microgram and PHE metaoblism a Km of 54 microgram, whereas in vitro the Km values were 330 microgram and 28 microgram respectively. 3 In vitro, MAO activity had substrate and inhibitor specificities compatible with the presence of A and B types of MAO. 4 In perfused lung, metabolism of 5-HT but not that of PHE was inhibited by desmethylimipramine. 5 These results show that PHE metabolism in perfused lung, unlike that of other metabolized amines, is not limited by transport and the transport process for PHE is unlike that of 5-HT or noradrenaline. 6 These results also show that the kinetic parameters obtained for MAO activity in vitro do not generally apply to the isolated lung where transport of substrate can be the deciding factor. This discrepancy emphasizes that the enzymic properties of the whole organ cannot relaibly be deduced from its enzymic content.

Animals↗

Central and peripheral catecholamines and phenylethanolamine-N-methyl-transferase activity during the oestrus cycle.

Natural variations in monoamine levels in the adrenal gland, whole brain, hypothalamus and plasma during the oestrus cycle were determined in Sherman rats. Noradrenaline content of adrenal gland was at its highest level during met-oestrus phase while adrenaline was at its lowest level. During pro-oestrus adrenaline in the adrenal gland was at the maximum value. Plasma adrenaline did not change significantly during the oestrus cycle. However plasma noradrenaline was significantly higher during metoesrus compared to the value of di-oestrus and pro-oestrus. In the hypothalamus noradrenaline level was at its highest value during di-oestrus and at its lowest during met-oestrus, while brian noradrenaline reached its maximum value during pro-oestrus. The sum of plasma adrenaline and noradrenaline showed maximum level during met-oestrus phase but at the same time total adrenal adrenaline plus noradrenaline was lowered. The variations in adrenaline and noradrenaline in the adrenal gland did not correspond to the changes in the activity of enzyme, phenylethanolamine-N-methyltransferase (PNMT). The activity of PNMT reached its maximum value during met-oestrus phase of the oestrus cycle. The observed variations in adrenal, brain, hypothalamus and plasma catecholamines can be attributed to the modification in endocrine activity which takes place during the oestrus cycle.

Adrenal Glands↗

Activity of catechol-o-methyltransferase in brain regions and adrenal gland during the oestrus cycle.

The activity of the enzyme catechol-O-methyltransferase (COMT) during four different phases of the oestrus cycle were determined. Brain and hypothalamus had highest level of COMT activity during oestrus phase, while at pro-oestrus it was at its lowest level. COMT activity in the adrenal gland was also modified during the four phases with the maximum level at met-oestrus and minimum at pro-oestrus phase. The results provide evidence to show that COMT in the brain, hypothalamus and the adrenals is markedly affected by changes in physiological status of the female rats and its evolution in brain is different from adrenal gland during the oestrus cycle. The variations in the activity of COMT may be the consequence of modified endocrine activity which takes place naturally during oestrus cycle.

Adrenal Glands↗

The effect of selective monoamine oxidase inhibitors, clorgyline and deprenyl, upon tissue glycogen stores and blood glucose levels.

The effect of selective monoamine oxidase (MAO) inhibitors clogyline and deprenyl upon glycogen stores in brain, heart and liver and upon blood glucose were examined for a possible link between the activity of the oxidase and metabolism of carbohydrates. The experiments were performed in normally fed rats and rats subjected to starvation for 24 hours. This study showed that selective inhibitors of MAO affect carbohydrate metabolism and that this may be the consequence of increased monoamines in the organs and circulation. However, there was no correlation between the selective inhibition of a particular form of MAO and glycogen metabolism.

Animals↗

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↗

Implications of combined treatment with 'Madopar' and L-deprenil in Parkinson's disease. A long-term study.

In a clinical trial the effect of L-deprenil, a selective irreversible inhibitor of monoamine oxidase (M.A.O.) "type B" in potentiating the anti-kinetic properties of levodopa has been investigated in 223 patients. Both drugs were given orally, levodopa as 'Madopar' (levodopa plus the peripherally acting decarboxylase inhibitor, benserazide) 250 mg three times daily and L-deprenil 5 mg once or twice daily. The addition of L-deprenil to madopar therapy resulted in a statistically significant (P less than 0-01-0-001) reduction in patients' functional disability on average within 60 min after a single oral dose and lasting for 1 to 3 days. Dyskinesia occurred in 16 patients, psychosis in 14, orthostatic hypotension in 5, and nausea in 8. Reduction of the L-deprenil dose to 5 mg in these patients eliminated some of the side-effects. Two-thirds of the patients with side-effects had suffered from parkinsonism for between 7 and 15 years. 14% of the patients failed to respond to madopar-deprenil therapy. It is suggested that L-deprenil may act through inhibition of brain M.A.O. as well as by a psychostimulant effect similar to that of amphetamine which occurs through the release of dopamine. Both mechanisms would make more dopamine available at dopamine receptor sites.

Administration, Oral↗

Pica hypothesis.

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Humans↗