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Antidepressants: Pharmacology and Biochemistry

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NeuroPsychopharmacotherapy

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Abstract

The first antidepressants, discovered in the 1950s, and any successors directly target the monoaminergic brain systems. Problems in this group, however, are low effectiveness (only two-thirds of those treated responded to the therapy) and a significantly delayed onset of action of weeks to months. New findings on the pathophysiology of depression affecting the GABAergic and glutamatergic systems give hope for the development of rapid-acting and effective antidepressants.

Only understanding the basics of antidepressant pharmacotherapy makes it possible to comprehend new research approaches in this field. Moreover, the specialist knowledge makes it easier for clinicians to make an adequate and rational choice of the pharmaceuticals they use. By knowing the mechanism of action and the route of decomposition of the antidepressant selected, adverse drug reactions can be anticipated and avoided wherever possible.

For the reasons mentioned above, already known antidepressants (tricyclics, SSRI, SNRI, NRI and MAO inhibitors), as well as newer antidepressant-acting candidates (ketamine, scopolamine, rapastinel), will be discussed in this chapter with regard to their pharmacology and biochemistry.

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Abbreviations

5-HT:

5-hydroxytryptamine/serotonin

5-HT1A/5-HT1D/5-HT2/5-HT2A/5-HT2C/5-HT3:

Serotonin receptors; subtypes 1A/1D/2/2A/2C/3

α1/α2/β:

Adrenergic receptors; subtypes α1/α2/β

AC:

Adenylate cyclase

Akt:

Protein kinase B

AMP:

Adenosine monophosphate

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ATP:

Adenosine Triphosphate

BDNF:

Brain-derived neurotrophic factor

CA:

Cornu ammonis

Ca2+:

Calcium

CaMK:

Ca2+/calmodulin-dependent protein kinase

cAMP:

Cyclic adenosine monophosphate

Cl−:

Chloride

CNS:

Central Nervous System

COMT:

Catechol-O-methyltransferase

CREB:

cAMP response element-binding protein

D1/D2:

Dopamine receptors; subtypes 1/subtype 2

DA:

Dopamine

DDC:

DOPA decarboxylase

DG:

Dentate gyrus

DOPA:

L-3,4-dihydroxyphenylalanine/levodopa

DOPAC:

3,4-Dihydroxyphenylacetic acid

ECT:

Electroconvulsive therapy

eEF2:

Eukaryotic elongation factor 2

Ent:

Entorhinal cortex

FDA:

U.S. Food and Drug Administration

FST:

Forced swim test

GABA:

Gamma-Aminobutyric acid

GABAA:

GABA receptor; subtype A

H1:

Histamine receptor; subtype 1

HVA:

Homovanillic acid

Ki:

Inhibition constant

LH:

Lethargic mouse model

LHb:

Lateral habenula

LTP:

Long-term potentiation

M:

Muscarinic acetylcholine receptor

MAO-A/MAO-B:

Monoamine oxidase; subtypes A/B

MAPK:

Mitogen-activated protein kinase

MDD:

Major depressive disorder

mGluR2/3:

Metabotropic glutamate receptors; subtypes 2/3

mPFC:

Medial prefrontal cortex

MT:

Melatonin

MT1/MT2:

Melatonin receptors; subtypes 1/2

mTORC1:

Mammalian target of rapamycin complex 1

Na+:

Sodium

NDRI:

Norepinephrine dopamine reuptake inhibitor

NE:

Norepinephrine

NGF:

Nerve growth factor

NMDA :

N-Methyl-d-aspartic acid

nmol:

Nanomolar

NRI:

Selective norepinephrine reuptake inhibitor

NSFT:

Near the individual spatial frequency threshold

PDE-4:

Phosphodiesterase

PKA/PKC:

Protein kinases; subtypes A/C

PLC:

Phospholipase C

RNA:

Ribonucleic acid

RR:

Blood pressure

RCT:

Randomised controlled trial

Rsk:

Ribosomal s6 kinase

SNRI:

Serotonin norepinephrine reuptake inhibitor

SSA:

Succinate semialdehyde

SSRI:

Selective serotonin reuptake inhibitor

TCA:

Tricyclic antidepressant

TH:

Tyrosine hydroxylase

TrkB:

Tropomyosin receptor kinase B

Tyr:

Tyrosine

VGCC:

Voltage-gated Ca2+ channel

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Authors and Affiliations

  1. Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg-University Mainz, Mainz, Germany

    Vanessa Efinger & Kristina Friedland

  2. Institute of Pharmacology and Clinical Pharmacy, Goehte University Frankfurt, Frankfurt, Germany

    Walter E. Müller

Authors
  1. Vanessa Efinger
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  2. Walter E. Müller
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  3. Kristina Friedland
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Corresponding author

Correspondence to Kristina Friedland .

Editor information

Editors and Affiliations

  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

Section Editor information

  1. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians University Munich, Munich, Germany

    Gerd Laux

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

    Gerd Laux

  3. Department of Psychiatry, Ludwig-Maximilians-University Munich, Munich, Germany

    Hans-Jürgen Möller

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Efinger, V., Müller, W.E., Friedland, K. (2022). Antidepressants: Pharmacology and Biochemistry. 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_26

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