Tryptamine Metabolism in Depression

1965 ◽  
Vol 111 (479) ◽  
pp. 993-998 ◽  
Author(s):  
A. Coppen ◽  
D. M. Shaw ◽  
A. Malleson ◽  
E. Eccleston ◽  
G. Gundy

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.

1967 ◽  
Vol 113 (505) ◽  
pp. 1407-1411 ◽  
Author(s):  
David Murray Shaw ◽  
Francis E. Camps ◽  
Eric G. Eccleston

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.


1960 ◽  
Vol 106 (445) ◽  
pp. 1533-1538 ◽  
Author(s):  
R. Middlefell ◽  
I. Frost ◽  
G. P. Egan ◽  
H. Eaton

Phenelzine, β-phenylethylhydrazine, of structural formula, is regarded as a potent, rapidly acting, long-lasting monoamine oxidase (M.A.O.) inhibitor. The administration of such compounds protects 5-hydroxytryptamine (serotonin) which is destroyed by M.A.O. 5-hydroxytryptamine is believed to act in the brain as a chemical mediator, the function of which is to control the pulsating action of oligodendroglial cells which supply the other brain tissues with nutrient. It has been suggested that a relative 5-hydroxytryptamine deficiency is the fundamental biochemical disorder of severe depressive states and that M.A.O. inhibitors such as phenelzine tend to promote restoration to more normal concentration and activity.


1997 ◽  
Vol 3 (1) ◽  
pp. 46-51 ◽  
Author(s):  
Eleni Palazidou

The development of the first effective antidepressants in the late 1950s marked a turning point in the treatment of depressive illness. In 1957 the monoamine oxidase inhibitor (MAOI) iproniazid was discovered by chance, while searching for new antituberculous drugs. One year later the tricyclic antidepressant (TCA) imipramine was introduced, having been developed originally as an antipsychotic. A number of other drugs were subsequently added to these two groups of antidepressants, which dominated the field for the next three decades.


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

2003 ◽  
Vol 37 (4) ◽  
pp. 464-468 ◽  
Author(s):  
Gordon Parker ◽  
Gordon Parker ◽  
Kay Parker

Objective: The Black Dog Institute seeks to address issues of relevance to the clinical management of those with a mood disorder. This overview considers the capacity of antidepressant drugs, and particularly the new classes, to induce manic switching in depressed patients. Method: Relevant literature is reviewed. Results: It is unclear whether antidepressant drugs from any of the classes induce switching in unipolar depressed patients. In bipolar depressed patients, the broad-spectrum tricyclic and monoamine oxidase inhibitor drugs present a clear risk of switching, the selective serotonin re-uptake inhibitors do not appear (at standard doses) to increase the risk, while the capacity of the dual action (serotonergic and noradrenergic) drugs to induce switching remains unestablished but may be slight. Conclusions: As switching induced by narrow action antidepressants does not appear to present a substantive causal risk, clinicians can have confidence in prescribing certain antidepressants for managing bipolar depression, and without any necessity to first prescribe a mood stabilizer to pre-empt switching.


1989 ◽  
Vol 4 (3) ◽  
pp. 175-181
Author(s):  
J.F. Lipinski ◽  
R.C. Alexander

SummaryThe authors have reviewed 13 published studies on methionine administration, usually in combination with a monoamine oxidase inhibitor (MAOI), to chronically psychotic patients, using modern (DSM-III) diagnostic criteria. Four of these studies contained sufficient descriptive data to allow reappraisal of the effects. The results of the review suggest that a proportion of the patients experienced the induction of a manic episode/antidepressant effects rather than the reported worsening of schizophrenia while treated with a methionine-MAOI combination. It is suggested that these observations are consistent with recent findings that S-adenosyl-L-methionine (SAMe) has antidepressant and mania-inducing effects.


1995 ◽  
Vol 22 (s1) ◽  
pp. S86-S87 ◽  
Author(s):  
N. Hamaue ◽  
T. Endo ◽  
M. Hirafuji ◽  
N. Yamazaki ◽  
H. Togashi ◽  
...  

2010 ◽  
Vol 3 (4) ◽  
pp. 213-215
Author(s):  
Junji Takeshita ◽  
Deborah Goebert ◽  
John Huh ◽  
Brett Lu ◽  
Diane Thompson ◽  
...  

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