Chapter Category: Neuropharmacology

From the book Selective Serotonin Reuptake Inhibitors (SSRIs): Past Present and Future

The Discovery of The SSRIs: A Milestone In Neuropsychopharmacology and Rational Drug Design

Arvid Carlsson

Besides being a major therapeutic advance, the selective serotonin reuptake inhibitors (SSRIs) have become important tools in basic and clinical brain research. They were the first drugs to establish beyond doubt a pathophysiological role for serotonin (5-HT) in affective illnesses and in the broad spectrum of anxiety disorders. Likewise, the SSRIs were the first to confirm the inhibition of neurotransmitter reuptake as an important therapeutic principle. As a result, the discovery of these agents marks a milestone in neuropsychopharmacology and rational drug design. Below is an account of the fascinating, winding path of research leading to the SSRIs. The antidepressant action of imipramine was discovered in 1957 by Kuhn. At first pharmacologists were taken aback because this action was entirely unpredicted. In 1959 Sigg demonstrated that imipramine can potentiate the effects of noradrenaline as well as the response to sympathetic nerve stimulation. This was the first clue to the elucidation of the mode of action of imipramine. In 1960 Burn and Rand described the uptake of noradrenaline by adrenergic nerves. Cocaine was reported to block this uptake. In the same year, Marshall et al reported that the uptake of 5-HT by platelets could be blocked by imipramine and, in 1961, Axelrod et al described the uptake of labeled noradrenaline by adrenergic nerves. This uptake could be blocked by imipramine, cocaine and reserpine. At the same time Dengler et al reported similar data regarding noradrenaline uptake by brain tissue.

Taken from the book

Selective Serotonin Reuptake Inhibitors (SSRIs): Past Present and Future

Edited by: Arvid Carlsson

More chapters from the book:

Besides being a major therapeutic advance, the selective serotonin reuptake inhibitors (SSRIs) have become important tools in basic and clinical brain research. They were the first drugs to establish beyond doubt a pathophysiological role for serotonin (5-HT) in affective illnesses and in the...


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