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Synaptic Effects of Antidepressants
Abstract
Catecholamines, especially norepinephrine (NE) and serotonin (5-hydroxytryptamine [5-HT]), have been implicated in the pathophysiology of depression. However, their exact roles and their interrelationship are not completely understood. Antidepressants have various effects on the body, including action at the neuronal synapses of the brain; the two most important of these effects are blockade of the reuptake of neurotransmitters, including NE, 5-HT, and dopamine, and blockade of certain neurotransmitter receptors. Currently available antidepressants may be classified as inhibitors of monoamine oxidase or as blockers of biogenic amine neurotransmitter reuptake, the latter best describing tricyclic antidepressants and selective 5-HT-reuptake inhibitors, because they block the reuptake of one or more neurotransmitters. However, recently introduced antidepressants, such as the 5-HT-NE-reuptake inhibitors, have synaptic effects that differ from those of older compounds. These synaptic effects are important in explaining certain side effects and drug-drug interactions associated with all classes of antidepresants. This article reviews the synaptic effects of marketed antidepressant agents to elucidate the anticipated side effects and drug-interaction potential of these agents.
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SSRIs potently inhibit presynaptic uptake of serotonin, while exerting relatively weak effects on other neurotransmitter/receptor systems.
“Pharmacologically, the SSRIs potently inhibit presynaptic uptake of serotonin, while exerting relatively weak effects on other neurotransmitter/receptor systems [Richelson, 1996].”
From Depression, sleep physiology, and antidepressant drugs (2001) · cites this paper as Richelson, 1996
Trazodone and nefazodone are relatively weak inhibitors of presynaptic uptake of serotonin, exhibiting substantially smaller effects than the SSRIs.
“Both compounds are relatively weak inhibitors of presynaptic uptake of serotonin, exhibiting substantially smaller effects in this regard than the SSRIs [Richelson, 1996].”
From Depression, sleep physiology, and antidepressant drugs (2001) · cites this paper as Richelson, 1996
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Research works printed but not linked: 8
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- Richelson, 1984, Eur J Pharmacol, 104, 277, 10.1016/0014-2999(84)90403-5 · DOI
- Bolden-Watson, 1993, Life Sci, 52, 1023, 10.1016/0024-3205(93)90194-8 · DOI
- Richelson, 1984, J Pharmacol Exp Ther, 230, 94
- Cusack, 1994, Psychopharmacology, 114, 559, 10.1007/BF02244985 · DOI
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Cited by
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Kemp, A. H., Quintana, D. S., Gray, M. A., Felmingham, K. L., Brown, K., & Gatt, J. M. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.12.012 · Cited by 1,286
Pharmacological profile of antidepressants and related compounds at human monoamine transporters
Tatsumi, M., Groshan, K., Blakely, R. D., & Richelson, E. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(97)01393-9 · Cited by 939
Self-citationStahl, S. M., Pradko, J., Haight, B. R., Modell, J. G., Rockett, C. B., & Learned-Coughlin, S. (2004) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.v06n0403 · Cited by 495
Nebes, R. D., Pollock, B. G., Houck, P. R., Butters, M. A., Mulsant, B. H., Zmuda, M. D., & Reynolds, C. F. (2003) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(02)00085-7 · Cited by 275
Michelson, D., Fava, M., Amsterdam, J., Apter, J., Londborg, P., Tamura, R., & Tepner, R. G. (2000) · British Journal of Psychiatry · doi:10.1192/bjp.176.4.363 · Cited by 181
Depression, sleep physiology, and antidepressant drugs
Winokur, A., Gary, K. A., Rodner, S., Rae-Red, C., Fernando, A. T., & Szuba, M. P. (2001) · Depression and Anxiety · doi:10.1002/da.1043 · Cited by 179
Review: problems associated with long-term treatment with selective serotonin reuptake inhibitors
Moret, C., Isaac, M., & Briley, M. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881108093582 · Cited by 135
Metadata
- Authors
- RICHELSON, E.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- RICHELSON, ELLIOTT
- Venue
- Journal of Clinical Psychopharmacology
- Published
- 1996-06
- Volume
- 16
- Issue
- SUPPLEMENT 2
- Pages
- 1S-7S
- ISSN
- 0271-0749 (ISSN-L)
- OpenAlex
- W2069942756
- Cited by
- 120
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 1 · 2020: 1 · 2019: 3 · 2017: 2 · 2016: 3 · 2015: 3 · 2013: 6 · 2012: 1
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- antidepressants, norepinephrine, serotonin, dopamine, monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, antidepressant side effects, drug-drug interactions, depression pathophysiology
- MeSH terms
- Animals, Antidepressive Agents, Depressive Disorder, Dopamine, Drug Interactions, Humans, Synaptic Transmission, Norepinephrine, Serotonin, Synapses, Receptors, Neurotransmitter
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