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Antidepressants: Molecular Aspects of SSRIs

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NeuroPsychopharmacotherapy

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Abstract

Major depressive disorders are among the most common psychiatric diseases featuring an insufficient serotonin signaling as the most prominent core patho-mechanism. Therefore, selective serotonin re-uptake inhibitors are firstly employed to restore serotonin neurotransmission in depressed patients. One member of this class of antidepressants, which selectively targets the serotonin transporter, is citalopram. Citalopram was first synthesized in 1972 and consists of equal molecular amounts of the isomers R-citalopram and S-citalopram, generally referred to as escitalopram, which exerts the antidepressant effect. Underlying citalopram’s mode of action is an allosteric mechanism, by which citalopram modulates its own binding to the primary binding site at the serotonin transporter. The following chapter will provide an overview of recent findings on the molecular binding characteristics determining citalopram’s docking to the serotonin transporter and the allosteric modulation of the citalopram-induced antidepressant response. Here, the focus will be on the acute citalopram-induced effects, which result in dose-dependent internalization of serotonin transporter molecules and diminished neuronal activity of serotonergic neurons.

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Authors and Affiliations

  1. Integrative and Clinical Neurosciences EA481, University of Bourgogne Franche-Comté, Besançon, France

    Adeline Etievant

  2. Stem Cell and Brain Research Institute, INSERM, U1208, Bron, France

    Nasser Haddjeri

  3. Université de Lyon, Université Lyon 1, Lyon, France

    Nasser Haddjeri

  4. Central Institute of Mental Health, Department of Translational Brain Research, Medical Faculty Mannheim; Heidelberg University, Hector Institute for Translational Brain Research, Mannheim, Germany

    Thorsten Lau

  5. German Cancer Research Center (DKFZ), Heidelberg, Germany

    Thorsten Lau

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  1. Adeline Etievant
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  2. Nasser Haddjeri
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  3. Thorsten Lau
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Correspondence to Thorsten Lau .

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  1. Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Wuerzburg, Germany

    Peter Riederer

  2. Institute of Psychological Medicine (IPM), Soyen, Germany

    Gerd Laux

  3. Centre for Research Promotion and Support, Fujita Health University, Toyoake, Aichi, Japan

    Toshiharu Nagatsu

  4. Center Translational Res Neurol Diseases, Dalian Med Uni Shanghai Inst Health Sc Center Translational Res Neurol Diseases, Dalian, China

    Weidong Le

  5. Würzburg, Germany

    Christian Riederer

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  1. University Hospital, Center for Mental Health, Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Wuerzburg, Wuerzburg, Germany

    Peter Riederer

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Etievant, A., Haddjeri, N., Lau, T. (2022). Antidepressants: Molecular Aspects of SSRIs. In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-030-62059-2_369

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