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Arvid Carlsson (1923–2018)
Published in Andrew P. Wickens, Key Thinkers in Neuroscience, 2018
Two other discoveries by Carlsson must also be briefly mentioned. First, in the late 1960s, Carlsson showed that tricyclic antidepressants not only blocked the reuptake of NA (as had been shown by Axelrod) but also of 5-HT as well. This would lead him to develop the first 5-HT uptake inhibitor called Zimelidine, which became the forerunner of many more selective 5-HT uptake blockers such as fluoxetine (Prozac) developed by the drug company Eli Lilly. Second, in the early 1970s, pharmacological research began to point to the possibility of receptors located on the presynaptic endings of catecholamine neurons that acted to regulate the release of their own neurotransmitters. Carlsson supported this theory by showing that the synthesis of dopamine was inhibited by certain dopaminergic receptor agonists and stimulated by antagonists. In 1975, Carlsson used the term autoreceptors to refer to this specialised presynaptic receptor – a word that has now become widely adopted. It is also now recognised that changes in autoreceptor function play a particularly significant role in the pharmacological action of many antidepressant drugs.
Pharmacotherapy of Anxiety Disorders
Published in Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen, Handbook of Depression and Anxiety, 2003
David S. Baldwin, David Bridle, Ekelund Anders
In the first randomized controlled trial (n = 44) of an SSRI in panic disorder, zimelidine was found to be more efficacious than either placebo or imipramine [4]. Unfortunately, zimelidine was later associated with the development of a disorder similar to Guillain-Barre syndrome, and was withdrawn from clinical use [5].
Clinical pharmacological innovation in the treatment of depression
Published in Expert Review of Clinical Pharmacology, 2023
Jeffrey M Witkin, Lalit K Golani, Jodi L Smith
A general listing of FDA-approved antidepressants is shown in Table 2 and their structures are shown in Figure 1 – see [21] for a comprehensive review of conventional treatments. In the United States, SSRIs or SNRIs are generally the first-line therapy for MDD and for patients reporting depression symptoms to their primary care physicians. They are safe and most are generic and therefore mostly supported by payers. There are now many SSRI and SNRI compounds approved for MDD patients with zimelidine from Astra being the first to be approved (Fig. S1). These compounds increase the synaptic availability of monoamines, hypothesized to be involved in MDD symptoms – the monoamine hypothesis of depression [21].