Search PubMed⌕ Search

Biomedical subjects

V Glover

Publications and source records attributed to V Glover.

At least 181 records · Page 10Linked to original sources
PubMed1980

Dopamine oxidation and its inhibition by (-)-deprenyl in man.

Dopamine is predominantly oxidized by a (-)-deprenyl sensitive form of MAO in the human striatum, and (-)-deprenyl, acting at some suitably low selective inhibitory concentration may, therefore, be of benefit in Parkinson's disease. 10(-6)M was the most effective (-)-deprenyl concentration in vitro for discriminating between the inhibition of MAO A and B. The correlation between the A/B ratio present in different human brain regions and the sensitivity of dopamine oxidation to 10(-6)M deprenyl was 0.84 (p<0.001). This suggests that all dopamine oxidation can be accounted for by the joint contribution of MAO A and B and that it is unnecessary to postulate a special form of the enzyme which metabolizes dopamine. In the brain, the striatum has the highest proportion of MAO B, and in several cortical regions, relatively more dopamine is oxidized by MAO A. In other human tissues also the deprenyl sensitivity of dopamine oxidation correlated with the known A/B ratio, the placenta, lung and jejeunum having the lowest sensitivity and being the richest in MAO A. Km values for dopamine for MAO A and B are similar, 130 and 140 uM respectively, so that the proportion oxidized by the two forms should not vary with substrate concentration.

Blood Platelets↗
PubMed1980

Tele-Methylhistamine is a specific MAO B substrate in man.

Tele-methylhistamine, the first metabolite of histamine in tissues which lack diamine oxidase, is shown to be a substrate for human MAO B. Human liver homogenates were incubated with 3H-tele-methylhistamine and the products separated using thin-layer chromatography. The major product was 3-methylimidazoleacetic acid, the oxidatively deaminated metabolite of tele-methylhistamine. The reaction was inhibited by low concentrations of (-)deprenyl, the specific MAO B inhibitor. Tele-methylhistamine was also found to inhibit competitively the oxidation of phenylethlamine, but not that of 5-hydroxytryptamine, providing further evidence that it is oxidized by MAO B itself and not a related enzyme. This finding implies that (-)deprenyl and other MAO inhibitors used clinically may interfere with histamine metabolism.

Binding, Competitive↗
PubMed1980

The inhibition of tyramine oxidation and the tyramine hypertensive response ("cheese effect") may be independent phenomena.

Although the selective monoamine oxidase (MAO) inhibitor, (-)-deprenyl, substantially inhibits tyramine-oxidizing ability in the pig, intravenous tyramine challenge after pretreatment with this drug failed to produce the characteristic pressor response ("cheese effect") associated with other irreversible MAO inhibitors. Conversely, pretreatment with the tyramine oxidation-sparing selective MAO inhibitor, clorgyline, followed by intravenous tyramine, paradoxically resulted in a profound pressor response. We suggest that the action of standard MAO-inhibiting drugs may be compounded of two separate actions, usually associated but, in fact, unreleated.

Animals↗
PubMed1980

Further light on the tyramine test in depression.

In studies of post-partum women, the oral tyramine loading test is shown to be of predictive value in identifying those subjects with a lifetime history of depressive illness. The cause of the decreased output of conjugated tyramine, after tyramine ingestion, is still unclear. Some possible mechanisms have been under scrutiny.

Affective Disorders, Psychotic↗
PubMed1980

Platelet monoamine oxidase activity in megaloblastic anaemia.

Platelet monoamine oxidase activity has been measured in 17 patients with megaloblastic anaemia due to either vitamin B12 or folate deficiency, and in 20 healthy subjects. There was a highly significant increase in patients compared with controls. In two patients, platelet activity decreased following successful treatment. A significant correlation between platelet activity and the severity of bone marrow megaloblastic change, assessed by the deoxyuridine suppression test and bone marrow morphology, was also observed. If the change in activity also occurs in the nervous system, this may contribute to the mental disturbance associated with vitamin B12 or folate deficiency.

Anemia, Macrocytic↗
PubMed1979

A coupled peroxidatic oxidation technique for the histochemical localization of monoamine oxidase A and B and benzylamine oxidase.

A coupled peroxidatic oxidation technique is presented which employs benzylamine and tyramine as substrates and clorgyline, deprenyl, phenelzine and pargyline as specific inhibitors. Using this technique with frozen sections of human term placenta and rat liver, the histochemical localization of monocamine oxidase A and B and bnezylamine oxidase has been demonstrated.

Animals↗
PubMed1979

Monoamine mechanisms in chronic schizophrenia: post-mortem neurochemical findings.

Dopamine and its metabolites homovanillic acid and dihydroxyphenylacetic acid, noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid, and tryptophan and its metabolite kynurenine have been assayed in 9 schizophrenic and 10 control brains, together with the monoamine-related enzymes tyrosine hydroxylase monoamine oxidase, dopamine-beta-hydroxylase, and catechol-o-methyl-transferase. In schizophrenic brains dopamine, noradrenaline and serotonin were significantly increased in some areas of corpus striatum, but there were no significant changes in enzyme activity or monoamine metabolite concentrations in any of the brain areas examined. The findings are not consistent with theories that serotonin or noradrenaline stores are grossly depleted or noradrenaline neurones have degenerated, or that monoamine oxidase activity is abnormal, in schizophrenia, and provide no direct support for the hypothesis that dopamine neurones are overactive.

Aged↗
PubMed1978

Deprenyl administration in man: a selective monoamine oxidase B inhibitor without the 'cheese effect'.

After pretreatment with the selective monoamine oxidase B inhibitor, (-)-deprenyl, in doses sufficient for complete inhibition of the platelet enzyme, 4 normal and 6 parkinsoniam volunteers (2 receiving levodopa and 2 levodopa plus carbidopa) suffered no adverse pressor reaction ('cheese effect') after challenge with oral tyramine in amounts considerably greater than those likely to be encountered in a normal diet. Nor did the levodopa-deprenyl combination itself result in a pressor response. Normal human intestinal mucosa was shown predominantly to contain the deprenyl-insensitive A form of the enzyme, which presumably degraded administered tyramine in the deprenyl-treated volunteers; even those receiving the drug for prolonged periods manifested no 'cheese effect', suggesting that the A form remained uninhibited. Intestinal monoamine oxidase A was able to oxidise dopamine, whereas in human platelet or striatum the amine is a monoamine oxidase B substrate. Like tyramine, oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.

Adult↗
PubMed1978

Absence of "cheese effect" during deprenyl therapy: some recent studies.

Although the selective monoamine oxidase (MAO) B inhibitor, (-)deprenyl, has been shown to be free from the "cheese effect" in man after tyramine challenge, the reason for this is far from clear: it may well be independent of the selective inhibitory action of the drug, for during chronic administration there is some evidence to suggest that both A and B forms of the enzyme are equally inhibited. By-passing the putative MAO A gut barrier in the pig (chosen because it possesses MAO B alone in all other tissues) by intravenous tyramine administration into the deprenyl-pretreated animal failed to provoke a pressor response, despite substantial MAO inhibition. Conversely, clorgyline (MAO A inhibitor) pretreatment, which resulted in minimal MAO inhibition, produced a profound hypertensive response, resembling that observed with the non-MAO-inhibiting drug, isoniazid. The most parsimonious explanation for these findings may be that two separate but closely associated pharmacological effects are normally found with "orthodox" MAO inhibitors, enzyme inhibition proper and facilitation of noradrenaline release from its binding sites during tyramine challenge.

Amphetamines↗