Agomelatine: Mechanism of action and pharmacological profile in relation to antidepressant properties
Open accessAbstract
Agomelatine behaves both as a potent agonist at melatonin MT1 and MT2 receptors and as a neutral antagonist at 5-HT2C receptors. Accumulating evidence in a broad range of experimental procedures supports the notion that the psychotropic effects of agomelatine are due to the synergy between its melatonergic and 5-hydroxytryptaminergic effects. The recent demonstration of the existence of heteromeric complexes of MT1 and MT2 with 5-HT2C receptors at the cellular level may explain how these two properties of agomelatine translate into a synergistic action that, for example, leads to increases in hippocampal proliferation, maturation and survival through modulation of multiple cellular pathways (increase in trophic factors, synaptic remodelling, glutamate signalling) and key targets (early genes, kinases). The present review focuses on the pharmacological properties of this novel antidepressant. Its mechanism of action, strikingly different from that of conventional classes of antidepressants, opens perspectives towards a better understanding of the physiopathological bases underlying depression.
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Agomelatine has been shown to positively affect sleep-related measures including REM and slow wave sleep and the quality of sleep, so it is likely to be particularly useful for anxiety patient populations with sleep-related symptoms including PTSD and OCD.
“Since agomelatine has been shown to positively affect sleep-related measures including REM and slow wave sleep and the quality of sleep (Buoli et al., 2017;Guardiola-Lemaitre et al., 2014;Levitan et al., 2015), it is likely to be particularly useful for anxiety patient populations with sleep-related symptoms including also PTSD and OCD (De Berardis et al., 2015).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Guardiola-Lemaitre et al., 2014
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Pitrosky, B., Kirsch, R., Malan, A., Mocaër, E., & Pévet, P. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.3.r812 · Cited by 97 · see citing works
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Self-citationAgomelatine reverses the decrease in hippocampal cell survival induced by chronic mild stress
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Self-citation5-HT2B-receptor antagonist LY-272015 is antihypertensive in DOCA-salt-hypertensive rats
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Self-citationRole of peripheral and spinal 5-HT2B receptors in formalin-induced nociception
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Self-citationEmerging Opportunities and Concerns for Drug Discovery at Serotonin 5-5-HT2B Receptors
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Sorted by citations
Sartori, S. B., & Singewald, N. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107402 · Cited by 236 · see citing works
Vadnie, C. A., & McClung, C. A. (2017) · Neural Plasticity · doi:10.1155/2017/1504507 · Cited by 199 · see citing works
Millan, M. J., Goodwin, G. M., Meyer-Lindenberg, A., & Ove Ögren, S. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.01.016 · Cited by 132 · see citing works
Self-citation
- Authors
- Guardiola‐Lemaitre, B., De Bodinat, C., Delagrange, P., Millan, M. J., Munoz, C., & Mocaër, E.
- Affiliations
- Servier Monde Suresnes Cedex France
- Institut de Recherches Internationales Servier (IRIS) Suresnes Cedex France
- Institut de Recherches Internationales Servier (France) (FR)
- Servier International Suresnes Cedex France
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2014-07-17
- Volume
- 171
- Issue
- 15
- Pages
- 3604-3619
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC4128060
- OpenAlex
- W1720079291
- Cited by
- 182
- References
- 157
- Citations by year
- 2026: 20 · 2025: 19 · 2024: 13 · 2023: 9 · 2022: 15 · 2021: 18 · 2020: 15 · 2019: 20 · 2018: 20 · 2017: 10 · 2016: 11 · 2015: 9 · 2014: 3
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- agomelatine, antidepressant mechanism, 5-HT2C receptor antagonism, hippocampal neurogenesis, synaptic remodeling, glutamate signalling, depression pathophysiology, newer antidepressants
- MeSH terms
- Acetamides, Animals, Antidepressive Agents, Anxiety, Circadian Rhythm, Depression, Humans, Naphthalenes, Anti-Anxiety Agents, Receptor, Melatonin, MT1, Receptor, Melatonin, MT2, Neurogenesis, Serotonin 5-HT2 Receptor Antagonists
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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