drugnerd | consciousness inhibitor

Isoniazid was the first chemical compound established as an antidepressant, in 1952, by Jean-Francois Buisson in France and Max Lurie in the United States, after it had come in to use for the treatment of tuberculosis. Izoniazid, and a derivative iproniazid, were observed to have a “psychostimulant” effect and to inhibit the enzyme Monoamine Oxidase. Nathan Kline and colleagues conducted the first trial to show a significant effect of iproniazid on depression in psychiatric patients. Kline approached Roche with what he called a “psychic energizer” and the first MonoAmine Oxidase Inhibitor (MAOI) was introduced as Marsilid. Sales grew massively in the following years, and others of the class were introduced by several drug companies, but adverse effects such as hypertension crisis related to food amines, and acute hepatic necrosis, curtailed their use.

The discovery that a tricyclic (“three ringed”) compound had a significant antidepressant effect was also first made in the early 1950s, by Roland Kuhn in a Swiss psychiatric hospital. By that time antihistamine derivatives were coming in to use to treat surgical shock and then as psychiatric neuroleptics. Although, in 1955, in the first parallel-group randomized control trial in psychiatry, reserpine was demonstrated to be more effective than placebo in alleviating anxious depression, neuroleptics were developing for use as sedatives and antipsychotics. In attempting to improve the effectiveness of one of them, chlorpromazine, in conjunction with the Geigy pharmaceutical company, Kuhn discovered that compound “G 22355″ (manufactured and patented in the US in 1951 by Häfliger and Schinder) had a beneficial effect in patients with depression with mental and motor retardation He first reported his findings on what he called a “thymoleptic” in 1955/56 and they gradually became established, resulting in the marketing of the first tricyclic antidepressant, imipramine, soon followed by variants.

These new drug therapies became prescription-only medications (POM) in the 1950s. It was estimated that no more than 50 to 100 people per million suffered from the kind of depression that these new drugs would treat and pharmaceutical companies were not enthusiastic.

source:Wiki Dictionary Link