In vivo-inhibition of serotonin synthesis in mouse brain by β-phenylethylhydrazine, an inhibitor of monoamine oxidase

Dubnick, Bernard; Leeson, Gerald A.; Phillips, George E.

doi:10.1016/0006-2952(62)90089-8

Cited by 18 publications

(4 citation statements)

References 13 publications

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“…3 ) . The latter data confirm a previous article that showed that phenelzine inhibited decarboxylation of exogenously administered 5-HTP (Dubnick et al, 1962).…”

Section: Discussionsupporting

confidence: 92%

Inhibition of Aromatic L‐Amino Acid Decarboxylase and Tyrosine Aminotransferase by the Monoamine Oxidase Inhibitor Phenelzine

Dyck

Dewar

1986

Journal of Neurochemistry

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The concentration of p‐tyramine in the rat striatum was increased significantly by intraperitoneal injection of phenelzine (5 or 100 mg/kg). Unlike other monoamine oxidase (MAO) inhibitors, phenelzine had no effect on p‐tyramine levels in the first 1–2 h following injection. The high dose of phenelzine increased the p‐tyramine levels much more than the low dose. In addition, the high dose of phenelzine increased striatal p‐tyrosine levels significantly 12 h after injection. Further studies showed that phenelzine inhibited the tyrosine amino‐transferase activity of rat liver homogenates; the IC50 was 50 μM. Phenelzine also inhibited the aromatic L‐amino acid decarboxylase activity of rat brain homogenate with an IC50 of 25 μM. Following intraperitoneal injection of 100 mg/kg phenelzine, the initial concentration of phenelzine in the striatum appears to be high enough to inhibit aromatic L‐amino acid decarboxylase. It is suggested that the multiple enzyme inhibition caused by administration of high doses of phenelzine accounts for its unusual effects on striatal p‐tyramine levels compared with other MAO inhibitors, i.e., its initial lack of effect on p‐tyramine levels followed later by very large increases in p‐tyramine levels.

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“…3 ) . The latter data confirm a previous article that showed that phenelzine inhibited decarboxylation of exogenously administered 5-HTP (Dubnick et al, 1962).…”

Section: Discussionsupporting

confidence: 92%

Inhibition of Aromatic L‐Amino Acid Decarboxylase and Tyrosine Aminotransferase by the Monoamine Oxidase Inhibitor Phenelzine

Dyck

Dewar

1986

Journal of Neurochemistry

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“…5 illustrates two pools of 5-hydroxytryptamine in the subcellular synthetic complex, one in which the 5-hydroxytryptamine is stored, probably as a nucleotide complex of the type proposed by Pletscher and co-workers (Berneis, Da Prada & Pletscher, 1969;Goetz, Da Prada & Pletscher, 1971) where turnover will be relatively slow and a second pool of newly synthesized 'free' 5-hydroxytryptamine which will turn over relatively rapidly and will give rise to the inhibitory feedback and functional release of 5-hydroxytryptamine and which may, in instances in which the catabolism of free 5-hydroxytryptamine is inhibited by monoamine oxidase inhibitors, overflow on to receptors which do not normally receive stimulation from 5-hydroxytryptamine. Inhibition of 5-hydroxytryptophan decarboxylase which has been shown to occur in brain after phenelzine treatment (Dubnick, Leeson & Phillips, 1962) cannot be of major importance in producing the present biochemical changes, as 5-hydroxytryptophan was never detectable even after tryptophan administration.…”

Section: Discussionmentioning

confidence: 81%

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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“…It must be borne in mind that phenelzine acts al the same time as 5-hydroxytryptophane decarboxylase inhibitor although its action is much weaker than that exerted upon monoamine oxidase (7,3). Its effect on tryptophane hydroxylase is negligible (3).…”

Section: Resultsmentioning

confidence: 99%

“…48 hours after the administration of phenelzine the original in crease of the yellow fluorescence was lower than that seen in 4-hour experiments. Yet the yellow fluorescence remained some what stronger in the cell bodies than in the nerve terminals, whereas the axons were no longer visible.The biological and biochemical assays invariably report the marked increase of 5-IIT in the homogenates of the whole brain or of its lower parts in different animal species employing the phenelzine dosage of the same order or higher (7,5,14). It must be borne in mind that phenelzine acts al the same time as 5-hydroxytryptophane decarboxylase inhibitor although its action is much weaker than that exerted upon monoamine oxidase (7, 3).…”

mentioning

confidence: 99%

Increase of Serotonin Levels in the Specific Serotonergic Neurons of Rat Brain Caused by Phenelzine

Bartoníček¹

1965

Pharmacology

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In vivo-inhibition of serotonin synthesis in mouse brain by β-phenylethylhydrazine, an inhibitor of monoamine oxidase

Cited by 18 publications

References 13 publications

Inhibition of Aromatic L‐Amino Acid Decarboxylase and Tyrosine Aminotransferase by the Monoamine Oxidase Inhibitor Phenelzine

Inhibition of Aromatic L‐Amino Acid Decarboxylase and Tyrosine Aminotransferase by the Monoamine Oxidase Inhibitor Phenelzine

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

Increase of Serotonin Levels in the Specific Serotonergic Neurons of Rat Brain Caused by Phenelzine

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