The effects of the anticonvulsant valproic acid on cerebral indole amine metabolism

1979 ◽  
Vol 57 (8) ◽  
pp. 843-847 ◽  
Author(s):  
V. MacMillan
Keyword(s):  
Valproic Acid ◽  
Cerebral Hemisphere ◽  
Transport Mechanism ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Decarboxylase Inhibitor ◽  
Amine Metabolism ◽  
Hydroxyindoleacetic Acid ◽  
The Brain ◽  
Tryptophan Hydroxylation

The effects of valproic acid (500 mg/kg, ip, 1 h prior to testing) on indole amine metabolism were studied in rats by measurement of the contents of tryptophan, 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebral hemisphere. Tryptophan and 5-HIAA levels were increased, whereas 5-HTP and 5-HT remained unchanged. Furthermore, valproic acid failed to alter the levels of 5-HTP and DOPA, 5-HT and DA, and 5-HIAA in animals pretreated, respectively, with 3-hydroxybenzyl hydrazine (a decarboxylase inhibitor), pargyline (a monoamine oxidase inhibitor), or probenecid (a compound which blocks 5-HIAA transport out of the brain and cerebrospinal fluid). These results militate against the possibility that valproic acid alters the rate of tryptophan hydroxylation or the synthesis of 5-HT. However they do support the concept that valproic acid increases brain 5-HIAA by inhibition of the transport mechanism which removes 5-HIAA from the brain.

The effects of imidazole-4-acetic acid on cerebral indole amine metabolism

1982 ◽  
Vol 60 (3) ◽  
pp. 308-312
Author(s):  
V. MacMillan
Keyword(s):  
Acetic Acid ◽  
Steady State ◽  
Monoamine Oxidase ◽  
Cerebral Hemisphere ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Serotonin Metabolism ◽  
Decarboxylase Inhibitor ◽  
Amine Metabolism ◽  
Hydroxyindoleacetic Acid

The effects of imidazole-4-acetic acid (IMA, 100–400 mg/kg) on indole amine metabolism were studied by measurement of the cerebral hemisphere and brain stem contents of tryptophan, 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA). The results indicated that IMA does not alter the steady-state contents of brain indole amines. Furthermore, IMA failed to alter the levels of 5-HTP, 5-HT, or 5-HIAA in animals pretreated with 3-hydroxybenzyl hydrazine (a decarboxylase inhibitor), pargyline (a monoamine oxidase inhibitor), or probenecid (a compound which blocks 5-HIAA transport out of brain). These results suggest that altered serotonin metabolism is not a factor in the genesis of the behavioral or electroencephalographic changes produced by IMA.

Catabolism of intracerebroventricularly injected 5-hydroxytryptamine in mouse: effect of coinjection of tryptamine and several pretreatments

1993 ◽  
Vol 71 (3-4) ◽  
pp. 201-204 ◽  
Author(s):  
B. Duff Sloley ◽  
Shuzo Orikasa ◽  
Alan A. Boulton
Keyword(s):  
Monoamine Oxidase ◽  
Receptor Antagonist ◽  
Mouse Brain ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Nerve Terminals ◽  
Intracerebroventricular Injection ◽  
Hydroxyindoleacetic Acid

The catabolism of intracerebroventricularly injected 5-hydroxytryptamine in mouse brain was investigated. Pretreatment of animals with the 5-hydroxytryptamine type 1 receptor antagonist metergoline, the 5-hydroxytryptamine type 2 receptor antagonist ketanserin, the 5-hydroxytryptamine reuptake inhibitor fluoxetine, or the selective 5-hydroxytryptamine neurotoxin 5,7-dihydroxytryptamine failed to alter the rate of catabolism of intracerebroventricularly administered 5-hydroxytryptamine. The monoamine oxidase inhibitor tranylcypromine effectively blocked degradation of injected 5-hydroxytryptamine and accumulation of 5-hydroxyindoleacetic acid. Coinjection of tryptamine with 5-hydroxytryptamine reduced the rate of conversion of 5-hydroxytryptamine to 5-hydroxyindoleacetic acid. These results indicate that intracerebroventricularly administered 5-hydroxytryptamine is removed by a monoamine oxidase dependent system. This catabolism is not affected by inhibition of presynaptic uptake, 5-hydroxytryptamine receptor type 1 or type 2 blockade, or destruction of serotonergic nerve terminals. The coadministration of tryptamine may prolong the residence period of 5-hydroxytryptamine through competition for monoamine oxidase.Key words: 5-hydroxytryptamine, tryptamine, monoamine oxidase, intracerebroventricular injection, catabolism.

scholarly journals Endogenous monoamine oxidase inhibitor in the brain and urine of SHRSP

1992 ◽  
Vol 33 (4) ◽  
pp. 573-573
Author(s):  
Masaru Minami ◽  
Naoya Hamaue ◽  
Yoshiki Kanamaru ◽  
Toru Endo ◽  
Yoshio Monma ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
The Brain

Tryptamine Metabolism in Depression

1965 ◽  
Vol 111 (479) ◽  
pp. 993-998 ◽  
Author(s):  
A. Coppen ◽  
D. M. Shaw ◽  
A. Malleson ◽  
E. Eccleston ◽  
G. Gundy
Keyword(s):  
Body Weight ◽  
Monoamine Oxidase ◽  
Previous Investigation ◽  
Monoamine Oxidase Inhibitor ◽  
Depressive Illness ◽  
Oxidase Inhibitor ◽  
Tryptophan Metabolism ◽  
Depressed Patients ◽  
Brain Amines ◽  
The Brain

In a previous investigation we showed that large doses of DL-tryptophan (214 mg./kg. body weight) given to depressed patients receiving tranylcypromine (a monoamine oxidase inhibitor) potentiated the antidepressive effects of the drug (Coppen, Shaw and Farrell, 1963). This procedure increases the level of brain 5-hydroxytryptamine (5 HT) and tryptamine in the rat (Hess and Doepfner, 1961). Reserpine reduces the level of these amines in the brain, and it is known that patients being treated for hypertension with this drug often become depressed. Thus there is evidence that increasing certain brain amines may alleviate, and depleting brain amines may induce, a depressive illness. We therefore decided to study tryptophan metabolism in depressed patients. The pathways with which we were concerned are shown below.

The effects of acute hypercapnia on cerebral indole amine metabolism

1978 ◽  
Vol 56 (2) ◽  
pp. 223-226 ◽  
Author(s):  
V. MacMillan
Keyword(s):  
Monoamine Oxidase ◽  
Cerebral Hemisphere ◽  
Tryptophan Hydroxylase ◽  
Monoamine Oxidase Inhibition ◽  
Decarboxylase Inhibition ◽  
Amine Metabolism ◽  
Hydroxyindoleacetic Acid ◽  
Oxidase Inhibition ◽  
Increased Activity ◽  
Synthesis And Degradation

The effects of 1-h exposure to hypercapnia ([Formula: see text], 90–110 mmHg) on cerebral indole amine metabolism were studied in rats by measurement of cerebral hemisphere contents of tryptophan, 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA). 5-HIAA content was increased after 1-h exposure to hypercapnia, whereas tryptophan, 5-HTP, and 5-HT remained unchanged from control. The accumulation of 5-HTP after decarboxylase inhibition with 3-hydroxybenzyl hydrazine was increased in hypercapnic rats and indicated an increased activity of tryptophan hydroxylase. During the 1-h exposure to hypercapnia there was increased accumulation of 5-HT after monoamine oxidase inhibition with pargyline and increased accumulation of 5-HIAA arter probenecid. The results indicate an increased synthesis and degradation of indole amines in acute hypercapnia.

Effects of chronic monoamine oxidase inhibitor treatment on biogenic amine metabolism in rat brain

1979 ◽  
Vol 18 (10) ◽  
pp. 771-776 ◽  
Author(s):  
D.S. Robinson ◽  
I.C. Campbell ◽  
Margaret Walker ◽  
Nancy J. Statham ◽  
W. Lovenberg ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Rat Brain ◽  
Biogenic Amine ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Amine Metabolism ◽  
Inhibitor Treatment

5-Hydroxytryptamine in the Hind-Brain of Depressive Suicides

1967 ◽  
Vol 113 (505) ◽  
pp. 1407-1411 ◽  
Author(s):  
David Murray Shaw ◽  
Francis E. Camps ◽  
Eric G. Eccleston
Keyword(s):  
Monoamine Oxidase ◽  
Enzyme Inhibitor ◽  
Monoamine Oxidase Inhibitor ◽  
Chronic Schizophrenia ◽  
Depressive Illness ◽  
Oxidase Inhibitor ◽  
Number Of Patients ◽  
The Central Nervous System ◽  
The Brain

There is growing evidence of a connection between the metabolism of monoamines and severe depressive illness, but the exact role of these substances in affective disorders has yet to be defined. We know that reserpine depletes the brain of monoamines and that a proportion of patients treated with this compound develop a depressive illness. Conversely a number of compounds which raise the levels of amines in the brain by blocking the enzyme monoamine oxidase have been used in antidepressant therapy. The knowledge that loss of amines may be associated with depression, and that their replenishment in the brain may induce recovery, immediately leads to the question as to which of the biogenic amines is responsible for the affective changes. Pollin, Cardon and Kety (1961) observed the effect of giving various amino acids together with a monoamine oxidase inhibitor (M.A.O.I.) to patients suffering from chronic schizophrenia. They found that only tryptophan, the precursor of the monoamine 5-hydroxytryptamine (5HT), produced an elevation of mood. On the basis of their results, Coppen, Shaw and Farrell (1963) treated a number of patients suffering from severe depressive illness with M.A.O.I. and half of this group also received an oral dose of a suspension of D L-tryptophan (214 mg./kg. body weight) for one week. The patients taking tryptophan and M.A.O.I. recovered more rapidly than those receiving M.A.O.I. alone both while they were on tryptophan and also subsequently. One explanation for these findings was that the combination of M.A.O.I. and tryptophan increased the amount of amines derived from tryptophan in the brain, and that it was this which was responsible for the therapeutic effect. If this were so, then there were several possibilities. The first was that the level of 5HT in the brain was low in depression and the combination of amine precursor and enzyme inhibitor brought it back to normal. Alternatively it may be that recovery occurred as a result of the presence of abnormally large quantities of 5HT in the central nervous system or even following the production of tryptamine, another amine derived from tryptophan.

Amine Metabolism after an Overdose of a Monoamine Oxidase Inhibitor

1962 ◽  
Vol 267 (9) ◽  
pp. 421-426 ◽  
Author(s):  
Eugene T. Baldridge ◽  
Leona V. Miller ◽  
Bernard J. Haverback ◽  
Shannon Brunjes
Keyword(s):  
Monoamine Oxidase ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Amine Metabolism

Determination of 5-hydroxytryptophan, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid in 20 rat brain nuclei using liquid chromatography with electrochemical detection

1983 ◽  
Vol 61 (5) ◽  
pp. 530-534 ◽  
Author(s):  
Thérèse Di Paolo ◽  
André Dupont ◽  
Pierre Savard ◽  
Michel Daigle
Keyword(s):  
Liquid Chromatography ◽  
Rat Brain ◽  
Electrochemical Detection ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Major Metabolite ◽  
Tissue Preparation ◽  
Brain Nuclei ◽  
Hydroxyindoleacetic Acid

High-performance liquid chromatography with electrochemical detection is utilized for the simultaneous determination of serotonin, its precursor 5-hydroxytryptophan, and its major metabolite 5-hydroxyindoleacetic acid in nervous tissue samples. Tissue preparation required only homogenization in acidic solution and centrifugation prior to application to the chromatograph. Detection limits in the low picogram range were obtained for those indoles separated. This assay was used in combination with a micropunch dissection technique of 20 discrete rat brain nuclei to measure serotonin, its precursor, and major metabolite. The specificity of the assay was checked with pharmacological experiments aimed to increase or decrease serotonin levels. Pargyline, a monoamine oxidase inhibitor, led to a marked increase in serotonin and a decrease of 5-hydroxyindoleacetic acid while p-chlorophenylalanine, by blocking the conversion of tryptophan to 5-hydroxytryptophan, selectively depleted 5-hydroxytryptophan, serotonin, and 5-hydroxyindoleacetic acid.

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