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Noradrenergic modulation of central serotonergic neurotransmission: acute and long-term actions of mirtazapine
Abstract
Mirtazapine (Org 3770, Remeron) is a new alpha2-adrenoceptor antagonist which is an effective antidepressant drug. An in vivo electrophysiological paradigm in the rat was used to assess the effects of acute and long-term treatment with mirtazapine on pre- and postsynaptic alpha2-adrenoceptors and to determine whether this drug can modulate serotonin (5-HT) neurotransmission. The acute administration of mirtazapine produced a rapid increase in both noradrenaline and 5-HT neurotransmission by blocking both alpha2-adrenergic auto- and heteroreceptors, resulting in an enhanced tonic activation of postsynaptic 5-HT receptors. Long-term administration showed that this tonic activation of postsynaptic 5-HT receptors was most likely enhanced after such a treatment, as a result of a sustained increase in 5-HT neuronal activity in the presence of and due to inactivated alpha2-adrenergic heteroreceptors.
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“The improvements in sleep with mirtazapine are more likely to be the result of 5-HT2 receptor inhibition (Haddjeri et al., 1995).”
From Antidepressants and their effect on sleep (2005) · cites this paper as Haddjeri et al., 1995
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Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission
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Antidepressants and their effect on sleep
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A double-blind, placebo-controlled study of antidepressant augementation with mirtazapine
Carpenter, L. L., Yasmin, S., & Price, L. H. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01262-8 · Cited by 244
A Double Blind Comparison of Venlafaxine and Paroxetine in Obsessive-Compulsive Disorder
Denys, D., van der Wee, N., van Megen, H. J. G. M., & Westenberg, H. G. M. (2003) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000095342.32154.54 · Cited by 151
Metadata
- Authors
- Haddjeri, N., Blier, P., & de Montigny, C.
- Affiliations
- McGill University (CA)
- ORCID
- Venue
- International Clinical Psychopharmacology
- Published
- 1995-12
- Volume
- 10
- Issue
- Supplement 4
- Pages
- 11-17
- ISSN
- 0268-1315 (ISSN-L)
- OpenAlex
- W1967404230
- Cited by
- 137
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2022: 51 · 2021: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 6 · 2013: 1 · 2012: 6
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International 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
- mirtazapine, noradrenergic modulation, serotonergic neurotransmission, alpha2-adrenoceptor antagonism, antidepressants, norepinephrine, long-term drug treatment
- MeSH terms
- Mirtazapine, Adrenergic alpha-Antagonists, Animals, Antidepressive Agents, Tricyclic, Brain, Depressive Disorder, Dose-Response Relationship, Drug, Hippocampus, Humans, Long-Term Care, Mianserin, Synaptic Transmission, Neurons, Norepinephrine, Receptors, Adrenergic, Receptors, Serotonin, Serotonin, Receptors, Adrenergic, alpha-2, Rats, Adrenergic alpha-2 Receptor Antagonists
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