Agonist and antagonist actions of yohimbine as compared to fluparoxan at α2‐adrenergic receptors (AR)s, serotonin (5‐HT)1A, 5‐HT1B, 5‐HT1D and dopamine D2 and D3 receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states

  title={Agonist and antagonist actions of yohimbine as compared to fluparoxan at $\alpha$2‐adrenergic receptors (AR)s, serotonin (5‐HT)1A, 5‐HT1B, 5‐HT1D and dopamine D2 and D3 receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states},
  author={Mark J Millan and Adrian Newman-Tancredi and Valérie Audinot and Didier Cussac and Françoise Lejeune and Jean Paul Nicolas and Francis Cogé and Jean Pierre Galizzi and Jean A. Boutin and Jean Michel Rivet and Anne Dekeyne and Alain P. Gobert},
Herein, we evaluate the interaction of the α2‐AR antagonist, yohimbine, as compared to fluparoxan, at multiple monoaminergic receptors and examine their roles in the modulation of adrenergic, dopaminergic and serotonergic transmission in freely‐moving rats. Yohimbine displays marked affinity at human (h)α2A‐, hα2B‐ and hα2C‐ARs, significant affinity for h5‐HT1A, h5‐HT1B, h5‐HT1D, and hD2 receptors and weak affinity for hD3 receptors. In [35S]GTPγS binding protocols, yohimbine exerts antagonist… 

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

In contrast to citalopram, mirtazapine reinforces frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission, and reflects antagonist properties at α2A‐AR and 5‐HT2C receptors.

Anticataleptic properties of α2 adrenergic antagonists in the crossed leg position and bar tests: differential mediation by 5-HT1A receptor activation

Serotonin 5-HT1A receptors play a prominent role in anticataleptic effects of certain α2 adrenergic antagonists in the CLP test, whereas α2-adrenergic mechanisms are likely to be primarily responsible for the anticatalesptic effects of these ligands in the bar test.

Discriminative stimulus properties of idazoxan: mediation by both α2 adrenoceptor antagonism and 5‐HT1A receptor agonism

Both α2 adrenoceptor antagonism and 5‐HT1A receptor agonism appear to contribute to the discriminative stimulus effects of idazoxan, and the role of 5‐ HT1A receptors agonism should be considered when evaluating the behavioral effects of idazxan.

Evaluation of the effects of α2 adrenoceptor antagonism with the D2 receptor antagonist raclopride on conditioned avoidance responding in rats

To the extent that 5-HT1A receptor antagonism failed to block the effects of idazoxan in combination with raclopride on CAR, α2 adrenoceptor antagonism alone appears to potentiate the putative antipsychotic effects produced through D2 receptors antagonism.

The α2-adrenoceptor antagonist atipamezole potentiates anti-Parkinsonian effects and can reduce the adverse cardiovascular effects of dopaminergic drugs in rats

Atipamezole improved the efficacy of L-DOPA and apomorphine in an animal model of Parkinson’s disease and also reduced adverse dopaminergic effects on vigilance and on cardiovascular function, suggesting that an investigation of the effects of specific α2-adrenoceptor antagonists in Parkinson's disease patients is warranted.

The role of α1- and α2-adrenoceptor subtypes in the vasopressor responses induced by dihydroergotamine in ritanserin-pretreated pithed rats

The results suggest that the DHE-induced vasopressor responses in ritanserin-pretreated pithed rats are mediated by α1- ( probably α1A, α1B and α1D) and α2- (probably α2A,α2B andα2C) adrenoceptors and may lead to the development of more selective antimigraine drugs devoid vascular side effects.

Yohimbine is a 5-HT1A agonist in rats in doses exceeding 1mg/kg.




Actions of α2 adrenoceptor ligands at α2A and 5-HT1A receptors: the antagonist, atipamezole, and the agonist, dexmedetomidine, are highly selective for α2A adrenoceptors

The agonist DMT and the antagonist atipamezole are the ligands of choice to distinguish α2-mediated from 5- HT1A-mediated actions, whilst several of the other compounds show only low or modest selectivity for α2A over 5-HT1A receptors; caution should be exercised in experimental and clinical interpretation of the actions of traditionally employed α2 ligands.

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

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.

Interaction between a selective 5‐HT1A receptor antagonist and an SSRI in vivo: effects on 5‐HT cell firing and extracellular 5‐HT

Pretreatment with the selective 5‐HT1A receptor antagonist, WAY 100635, blocked the inhibitory effect of paroxetine on5‐HT neuronal activity in the DRN and, at the same time, markedly enhanced the effect ofParoxetines on extracellular 5‐ HT in the FCx.

Potentiation of the Fluoxetine‐Induced Increase in Dialysate Levels of Serotonin (5‐HT) in the Frontal Cortex of Freely Moving Rats by Combined Blockade of 5‐HT1A and 5‐HT1B Receptors with WAY 100,635 and GR 127,935

5‐HT1A/1B antagonism may represent a novel strategy for the improvement in the therapeutic profile of 5‐ HT reuptake inhibitor antidepressant agents and that 5‐HT may be primarily involved in such interactions.

Serotonin 5‐HT1D Receptors in Human Prefrontal Cortex and Caudate: Interaction with a GTP Binding Protein

Findings are supportive of the presence of serotonin 5‐HT1D receptors in human prefrontal cortex and caudate which appear to be coupled to a GTP binding protein.

Effect of a selective 5‐HT reuptake inhibitor in combination with 5‐HT1A and 5‐HT1B receptor antagonists on extracellular 5‐HT in rat frontal cortex in vivo

The results suggest that selective 5-HT reuptake inhibitors may cause a large increase in 5‐HT in the frontal cortex when 5‐ HT autoreceptors on both the somatodendrites (5‐HT1A) and nerve terminals (5-HT1B) are blocked.

Modulation of the activity of central serotoninergic neurons by novel serotonin1A receptor agonists and antagonists: a comparison to adrenergic and dopaminergic neurons in rats.

With the exception of (-)-tertatolol, which behaved as a weak agonist, a very similar pattern of inhibition of 5-HT turnover was seen in the striatum, the hippocampus and the hypothalamus (DRN and median raphe nucleus) and the spinal cord, with the Striatum displaying the greatest sensitivity.

Induction of hypothermia as a model of 5-hydroxytryptamine1A receptor-mediated activity in the rat: a pharmacological characterization of the actions of novel agonists and antagonists.

Hypothermia is a highly specific and sensitive response to activation of postsynaptic 5-HT1A receptors, an interpretation supported by the observation that destruction of central 5- HT neurons with 5,7-dihydroxytryptamine failed to reduce 8-OH-DPAT-induced hypothermia (DIH).

Evaluation of the effects of a specific α2-adrenoceptor antagonist, atipamezole, on α1- and α2-adrenoceptor subtype binding, brain neurochemistry and behaviour in comparison with yohimbine

The α2-antagonist atipamezole blocked allα2-adrenoceptor subtypes at low doses, stimulated central noradrenergic activity and had only slight effects on behaviour under familiar conditions, but increased neophobia.