Inhibitors of monoamine oxidase and decarboxylase of aromatic amino acids

Pletscher, A.; Gey, K. F.; Burkard, W. P.

doi:10.1007/978-3-642-85467-5_12

Cited by 37 publications

(27 citation statements)

References 995 publications

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“…The hydrazine group of phenelzine is highly reactive and extensive review (Pletscher, Geoy & Burkard, 1966) of these types of drugs has reported them to inhibit very many enzymic mechanisms other than the monoamine oxidase. However, as the hydrazine type monoamine oxidase inhibitor, isocarboxazine does not appear to inhibit 5-HIAA egress from brain (MacLean et at., 1965) it would appear that the effect of phenelzine on the transport of 5-HIAA from brain and c.s.f.…”

Section: Discussionmentioning

confidence: 99%

Interaction in the cerebral metabolism of the biogenic amines. Effects of phenelzine on the cerebral metabolism of the 5‐hydroxyindoles in dog brain

Moir

1972

British J Pharmacology

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Summary Chronic administration of phenelzine to dogs caused 5‐hydroxyindol‐3‐ylacetic acid (5‐HIAA) concentrations in c.s.f. from the lateral ventricle to be maintained at 50% of their normal values, but did not alter the concentrations of 5‐HIAA in c.s.f. from the cisterna magna. Following 10 days treatment with phenelzine, the active transport of 5‐HIAA from c.s.f. which normally occurs in the region of the fourth ventricle, was inhibited. This transport system was also inhibited by the addition of phenylacetic acid, the acid metabolite of phenelzine, to the fluid perfusing the cerebral ventricles. After 10–12 days treatment with phenelzine all regions of brain showed concentration increases to approximately 300% for 5‐HT and 150% for 5‐HIAA, but no alteration in the tryptophan concentration. Intravenous administration of tryptophan to dogs pretreated with phenelzine caused large increases in the concentration of tryptophan in brain and body fluids but did not alter either the concentrations of 5‐hydroxytryptamine and 5‐HIAA in brain or of 5‐HIAA in c.s.f. A model of the cerebral metabolism of 5‐hydroxytryptamine is proposed and the results are interpreted to mean that phenelzine has inhibitory actions, either directly or in some instances indirectly, on intracerebral tryptophan 5‐hydroxylase, monoamine oxidase and the transport of 5‐HIAA from both brain and c.s.f.

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Section: Discussionmentioning

confidence: 99%

Interaction in the cerebral metabolism of the biogenic amines. Effects of phenelzine on the cerebral metabolism of the 5‐hydroxyindoles in dog brain

Moir

1972

British J Pharmacology

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“…The atria from nialamide treated kittens exhibited diminished inotropic activity in response to direct and indirectly acting sympathomimetics. Monoamine oxidase inhibitors do not change or slightly decrease the catecholamine content of cat cardiac tissue (Bernheim & Bernheim, 1945;Goldberg & Shideman, 1962;Davey, Farmer & Reinert, 1963;Pletscher et al, 1966). A decrease in content is a possible explanation for the diminished responses observed with tyramine and amphetamine.…”

Section: Pressor Responses In Pithed Ratsmentioning

confidence: 99%

“…Monoamine oxidase inhibitors cause an increase in the content of monoamines in various tissues (Pletscher, Gey & Zeller, 1960;Crout, Creveling & Udenfriend, 1961;Spector, 1963;Pletscher, Gey & Burkard, 1966). The potentiation of the actions of indirectly acting sympathomimetic amines by monoamine oxidase inhibitors could therefore be caused by the release of greater amounts of noradrenaline from the increased store.…”

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confidence: 99%

The Mechanism of the Augmentation of Responses to Indirectly Acting Sympathomimetic Amines by Monoamine Oxidase Inhibitors

Rand

Trinker

1968

British Journal of Pharmacology and Chemotherapy

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“…In this study we investigated the effect of tranylcypromine 1 and pyrogallol, potent inhibitors of monoamine oxidase (32,33) and catechol-O-methyl transferase (8), respectively, on the response of the canine saphenous vein to adrenergic stimulation and on the pattern of venomotor responses to local temperature changes. The data suggest that the effect of local temperature changes cannot be explained by interference with the local action of the enzymes because, after inhibition of these enzymes, the dependence of the venomotor reactions on the local temperature was unchanged.…”

mentioning

confidence: 99%

Activity and Thermosensitivity of Canine Cutaneous Veins after Inhibition of Monoamine Oxidase and Catechol-O-Methyl Transferase

Vanhoutte

Shepherd

1969

Circulation Research

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The lateral saphenous vein of the dog was perfused with homologous blood at constant flow. Changes in driving pressure were used to measure active changes in venous tone. Administration of tranylcypromine greatly reduced the activity of monoamine oxidase in the vein and increased its response to electric stimulation of the lumbar sympathetic chain and to norepinephrine infusions. Administration of pyrogallol (a catechol-O-methyl transferase inhibitor) also increased the response of the vein to adrenergic stimulation. These chemicals did not alter the increase in the sensitivity of the venous smooth muscle to sympathetic nerve impulses and infused norepinephrine produced by cooling the perfusate. Thus, the potentiating effect of local cooling on the response of the cutaneous veins to adrenergic stimulation cannot be explained by interference with the local enzymatic inactivation of catecholamines.ADDITIONAL KEY WORDS tranylcypromine pyrogallol catecholamine inactivation local temperature and venous reactions increased venous response to adrenergic stimulation monoamine oxidase in veins• Webb-Peploe and Shepherd (1-3) have shown that the cutaneous veins of the intact dog are highly sensitive to local changes in temperature: cooling the blood perfusing them augmented the venomotor response to a constant adrenergic stimulation and warming depressed the response. It appeared that an alteration in the sensitivity of the venous smooth muscle to both endogenous catecholamines released by sympathetic nerve stimulation and exogenous infused norepinephrine accounted for the venous responses to local temperature changes (3). A logical explanation for this sensitizing effect could be that the local inactivation of catecholamines is inFrom the Section of Physiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55901.This investigation was supported in part by U. S. Public Health Service Research Grant HE-5883 from the National Heart Institute.Dr. Vanhoutte is a U. S. Public Health Service International Fellow on leave from the State University of Ghent, Belgium.Received March 13, 1969. Accepted for publication September 4, 1969. fluenced by temperature, as suggested by the longer-lasting phase of increase in perfusion pressure and the delayed relaxation observed with local cooling. However, the potentiation by cold could not be explained by inhibition of catecholamine reuptake at the nerve terminals (4).Another possible pathway for local inactivation of catecholamines, at different levels of the release-reuptake process, is enzymatic degradation by monoamine oxidase and catechol-O-methyl transferase (5-10), so that one could consider the hypothesis that local temperature changes may interfere with the local inactivation of catecholamines. Indeed, in different sympathetically innervated systems it appeared that inhibition of one or both of those enzymes resulted in an increase of the response to adrenergic stimulation (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Arteries and veins are reported to conta...

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Inhibitors of monoamine oxidase and decarboxylase of aromatic amino acids

Cited by 37 publications

References 995 publications

Interaction in the cerebral metabolism of the biogenic amines. Effects of phenelzine on the cerebral metabolism of the 5‐hydroxyindoles in dog brain

Interaction in the cerebral metabolism of the biogenic amines. Effects of phenelzine on the cerebral metabolism of the 5‐hydroxyindoles in dog brain

The Mechanism of the Augmentation of Responses to Indirectly Acting Sympathomimetic Amines by Monoamine Oxidase Inhibitors

Activity and Thermosensitivity of Canine Cutaneous Veins after Inhibition of Monoamine Oxidase and Catechol-O-Methyl Transferase

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