Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of α2‐adrenergic and serotonin2C receptors: a comparison with citalopram

@article{Millan2000MirtazapineEF,
  title={Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of $\alpha$2‐adrenergic and serotonin2C receptors: a comparison with citalopram},
  author={Mark J Millan and Alain P Gobert and Jean Michel Rivet and Agnes Adhumeau‐Auclair and Didier Cussac and Adrian Newman-Tancredi and Anne Dekeyne and Jean Paul Nicolas and Françoise Lejeune},
  journal={European Journal of Neuroscience},
  year={2000},
  volume={12}
}
Mirtazapine displayed marked affinity for cloned, human α2A‐adrenergic (AR) receptors at which it blocked noradrenaline (NA)‐induced stimulation of guanosine‐5′‐O‐(3‐[35S]thio)‐triphosphate ([35S]‐GTPγS) binding. Similarly, mirtazapine showed high affinity for cloned, human serotonin (5‐HT)2C receptors at which it abolished 5‐HT‐induced phosphoinositide generation. Alpha2‐AR antagonist properties were revealed in vivo by blockade of UK‐14,304‐induced antinociception, while antagonist actions at… Expand
Selective serotonin reuptake blockade increases extracellular dopamine in noradrenaline‐rich isocortical but not prefrontal areas: dependence on serotonin‐1A receptors and independence from noradrenergic innervation
TLDR
Investigation of the effects of citalopram and paroxetine and imipramine on extracellular NA and dopamine in the prefrontal cortex, parietal cortex and occipital cortex shows consistent with the existence of DA neurons separate from the NA ones contributing toextracellular DA even in NA‐rich/DA poor isocortical areas. Expand
Chronic citalopram administration desensitizes prefrontal cortex but not somatodendritic α2-adrenoceptors in rat brain
TLDR
Taken together, long‐term citalopram treatment induces a desensitization of &agr;2‐adrenoceptors acting as axon terminal autoreceptors in PFC without changes in somatodendritic andagr ;2‐ adrenoceptor sensitivity. Expand
Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation
TLDR
Results indicate that mirtazapine induces the enhancement of the output of cortical dopamine mediated via blockade of alpha(2)-adrenergic receptors and facilitation of post-synaptic 5-HT(1A) function. Expand
Interaction of the antidepressant mirtazapine with α2-adrenoceptors modulating the release of 5-HT in different rat brain regions in vivo
TLDR
The data confirm the basic α2-adrenoceptor-blocking properties of Mir, but are only partly concordant with previous studies reporting an increase of 5-HT output after Mir alone. Expand
S33005, a novel ligand at both serotonin and norepinephrine transporters: I. Receptor binding, electrophysiological, and neurochemical profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine.
TLDR
In conclusion, S33005 interacts potently with SERTs and, less markedly, with NETs and enhances extracellular levels of 5-HT and NE throughout corticolimbic structures and selectively elevates dialysis levels of DA in frontal cortex versus subcortical regions. Expand
Different actions for acute and chronic administration of mirtazapine on serotonergic transmission associated with raphe nuclei and their innervation cortical regions
TLDR
The results suggested that acute administration of mirtazapine probably activated serotonergic transmission, but its stimulatory action was abolished by activated inhibitory 5-HT1A receptor. Expand
Serotonin 5-HT3 receptor antagonism potentiates the antidepressant activity of citalopram
TLDR
The addition of a 5HT3R antagonist to SSRIs could represent a feasible strategy to improve antidepressant response and could enhance the antidepressant response of citalopram. Expand
Mirtazapine antagonises the subjective, hormonal and neuronal effects of m-chlorophenylpiperazine (mCPP) infusion: A pharmacological-challenge fMRI (phMRI) study
TLDR
The results suggest that mCPP-challenge phMRI produces reliable patterns of response that are mediated by 5-HT(2C) receptors; these responses may therefore be useful in-vivo measures of 5- HT( 2C) function in psychiatric disorders. Expand
A combination of mirtazapine and milnacipran augments the extracellular levels of monoamines in the rat brain
TLDR
Combined treatment with mirtazapine and milnacipran augments the extracellular levels of noradrenaline, serotonin and dopamine through the blockade of α(2) adrenoceptors without regional specificity, whereas mirtzapine enhances serotonergic transmission in a region-specific manner. Expand
Differential mechanisms underlie the regulation of serotonergic transmission in the dorsal and median raphe nuclei by mirtazapine: a dual probe microdialysis study
TLDR
The results suggest that enhanced serotonergic transmission resulting from α2 adrenoceptor blockade is offset by subsequent activation of 5-HT1A receptors and, in the DRN but not MRN, H1 receptor inhibition. Expand
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SummaryMirtazapine (Org 3770) is a selective antagonist at α2-adrenergic auto- and heteroreceptors, which are involved in regulation of neuronal noradrenaline (norepinephrine) and serotoninExpand
α2‐Adrenergic Receptor Blockade Markedly Potentiates Duloxetine‐ and Fluoxetine‐Induced Increases in Noradrenaline, Dopamine, and Serotonin Levels in the Frontal Cortex of Freely Moving Rats
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It is demonstrated that α2‐adrenergic receptors tonically inhibit NAD and DA and phasically inhibit 5‐HT release in the FCX and that blockade of α2 • receptors strikingly potentiates the increase in FCX levels of 5‐ HT, NAD, and DA elicited by reuptake inhibitors. Expand
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5‐HT2C receptors exert a tonic, suppressive influence on the activity of mesocortical — as well as mesolimbic and nigrostriatal — dopaminergic pathways, likely via indirect actions expressed at the level of their cell bodies. Expand
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The pharmacologic profile of mirtazapine.
Mirtazapine (Org 3770) is a new antidepressant with prominent alpha 2-adrenergic auto- and heteroreceptor antagonistic properties and no effect on monoamine reuptake. Mirtazapine increasesExpand
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TLDR
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