scholarly journals Development of new antidepressants

1997 ◽  
Vol 3 (1) ◽  
pp. 46-51 ◽  
Author(s):  
Eleni Palazidou
Keyword(s):  
Monoamine Oxidase ◽  
Turning Point ◽  
Monoamine Oxidase Inhibitor ◽  
Depressive Illness ◽  
Oxidase Inhibitor ◽  
Tricyclic Antidepressant ◽  
Antituberculous Drugs ◽  
One Year

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.

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 clinical relevance of treatment with antidepressants

1995 ◽  
Vol 7 (2) ◽  
pp. 52-54 ◽  
Author(s):  
W.A. Nolen
Keyword(s):  
Monoamine Oxidase ◽  
Clinical Relevance ◽  
Rating Scales ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Tricyclic Antidepressant ◽  
Statistical Evidence ◽  
Monoamine Oxidase A ◽  
Selective Serotonin ◽  
Uptake Inhibitors

Oince the discovery in the late 1950's of imipramine (Tofranil®), the first tricyclic antidepressant (TCA), and iproniazid, the first monoamine oxidase inhibitor (MAOI), many other TCAs and MAOIs, now being considered the classical antidepressants, have become available. Their effectiveness has been shown in numerous studies, although according to nowadays standards well designed studies (placebo-controlled, defined diagnostic groups, the use of standardized rating scales) with these compounds are relatively scarce.From the early 1980's the so called modern antidepressants have been introduced: the selective serotonin re-uptake inhibitors (SSRIs), the reversible selective monoamine oxidase-A inhibitors (RIMAs) and a variety of other compounds. All these drugs have been registered after their effectiveness had been shown in well designed, placebo-controlled studies. In defining the efficacy of antidepressants, registration authorities consider two aspects important: statistical evidence and clinical relevance.

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.

The treatment of anxiety disorders: a legacy of William Sargant

1997 ◽  
Vol 12 (8) ◽  
pp. 381-386
Author(s):  
MG Gelder
Keyword(s):  
Monoamine Oxidase ◽  
Anxiety Disorders ◽  
Mode Of Action ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Tricyclic Antidepressant ◽  
Psychological Treatments ◽  
Therapeutic Value ◽  
Chronic Anxiety ◽  
Made In

SummaryIn 1962 William Sargant and his colleagues described the therapeutic value of phenelzine, a monoamine oxidase inhibitor (MAOI), in chronic anxiety disorders and in the same year Klein and Fink reported the treatment of similar conditions with imipramine, a tricyclic antidepressant. Subsequent research has confirmed these findings and demonstrated the range of similar drugs that are effective in anxiety disorders. At the time of these original observations about the drug treatment of anxiety, there were no psychological treatments of proven value but in the intervening years much progress has been made in developing behavioural and cognitive procedures. The progress in determining the mode of action of these pharmacological and psychological treatments is reviewed and the implications of the findings are considered in relation to research into the causes of the anxiety disorders and to the treatment of patients.

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