At present, SSRIs and SNRIs are the first drugs of choice for most psychiatrists to treat depressive illness but the antidepressants also have an undeniable place in the management of depression. In , Kuhn used imipramine, which had a similar side chain as chlorpromazine, on patients with depressive psychosis and witnessed a remarkable improvement within a few weeks. The necessity to avoid this side effect resulted in the synthesis of selective inhibitors such as l-deprenyl selective, irreversible inhibitor of MAO-B and moclobemide selective, reversible inhibitor of MAO-A to avoid the fatal hypertensive crisis. The tricyclic antidepressants are derived from antihistaminic compounds, which were the predecessors of phenothiazines, the discovery of which was a revolution in the history of biological psychiatry. Nil Conflict of Interest:
National Center for Biotechnology Information , U. Later studies showed that its MAO-inhibiting property increased serotonin levels in the brain similar to the effects seen with 5-hydroxytrytophan, a precursor of serotonin, which crosses the blood-brain barrier. Recent developments in the design of antidepressant therapies: Later on, there were several reports of these drugs being associated with hepatotoxicity and death due to hypertensive crises and intracranial hemorrhages. The comparable effects of both MAO inhibitors and tricyclics led to the hypothesis by Sulser and Axelrod in that despite different mechanisms, the final mode of action was common, i. On the presence of 3-hydroxytyramine in brain.
Author information Copyright and License information Disclaimer. The effects were described as mood elevating. InHalfinger and Schindler, working at Geigy, synthesized 42 products from iminodibenzyl.
However, Mary Hare had observed similar results in with an enzyme, tyramine oxidase, which later was found to be MAO. The precursor of this drug was caee.
Antidepressants: From MAOIs to SSRIs and more
Kline, Loomer, and Saunders found a correlation between the effects of the antitubercular agents and their inhibitory action on MAO and used iproniazid for the first time on a group of patients with depression. Currently, MAO inhibitors are not first choice antidepressants, and are usually used only when there is intolerance or lack of response to the newer drugs, refractory depression or when ECT is contraindicated.
The mood elevating property of the drug, considered to be a side effect, became the primary effect in depression and heralded the synthesis of generations of newer antidepressants.
Depressive states during Rauwolfia therapy for arterial hypertension; a report of 30 cases. This article has been cited by other articles in PMC.
A CLINICAL AND BIOCHEMICAL STUDY OF A TRIAL OF IPRONIAZID IN THE TREATMENT OF DEPRESSION
Paper chromatography of urinary indoles. Open in a separate window. Guillain-Barre syndrome following zimeldine treatment. Kuhn’s observations were confirmed by other studies, including those of Lehmann who agreed with Kuhn cas the significance of imipramine in depressive illnesses.
InDeniker and Delay had a breakthrough with chlorpromazine as an effective antipsychotic.
Dopamine and tyramine were the substrates for both of the isomeric forms. National Center for Biotechnology InformationU. Ann Med Psychol Paris Mar; 3: John Wiley and Sons Inc; Get a printable copy PDF file cxse the complete article Kor click on a page image below to browse page by page.
Antidepressants: From MAOIs to SSRIs and more
Kuhn wanted to test the efficacy of G as an antipsychotic but was given G imipramine instead due to G’s intolerable side effects. Later on, there were several reports of ipronlazid drugs being associated with hepatotoxicity and death due to hypertensive crises and intracranial hemorrhages. Knowledge of brain function and of the neurobiology of depression has increased enormously in sstudy years and has increased awareness that the biogenic amines cannot be considered in isolation with regard to the etiology and pharmacotherapy of depression.
By chance, it was found to be an effective antitubercular agent. J Neurol Neurosurg Psychiatry.
Half a century of antidepressants: The above discoveries led to a new era in the development of psychotropics, i. Isonicotinyl hydrazine isoniazid was synthesized by Meyer and Malley at Prague from these hydrazine compounds. J Neurol Neurosurg Psychiatry.
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Five new SSRI antidepressants were designed by five different pharmaceutical companies[ 7 ]. It also shifted the focus of psychiatrists from psychodynamic processes to a biological basis of the illness. In the meantime, the enzyme MAO was reported by Johnston, into exist in two isomeric forms.
Full text Full text is available as a scanned copy of the original print version. Hence, Roland Kuhn iproniazod considered one of the pioneers in biological psychiatry and psychopharmacology.