The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

@article{Marek2005TheS5,
  title={The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine},
  author={Gerard J. Marek and Raúl Martı́n-Ruiz and Allyson Abo and Francesc Casa{\~n}as Artigas},
  journal={Neuropsychopharmacology},
  year={2005},
  volume={30},
  pages={2205-2215}
}
The addition of low doses of atypical antipsychotic drugs, which saturate 5-HT2A receptors, enhances the therapeutic effect of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) in patients with major depression as well as treatment-refractory obsessive-compulsive disorder. The purpose of the present studies was to test the effects of combined treatment with a low dose of a highly selective 5-HT2A receptor antagonist (M100907; formerly MDL 100,907) and low doses of a… 

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References

SHOWING 1-10 OF 58 REFERENCES

Synergistic Action of 5-HT2A Antagonists and Selective Serotonin Reuptake Inhibitors in Neuropsychiatric Disorders

Clinical and preclinical observations suggest that the combination of highly selective 5-HT2A antagonists and SSRIs, as well as strategies to combine high-potency 5- HT2A receptor and5-HT transporter blockade in a single compound, offer the potential for therapeutic advances in a number of neuropsychiatric disorders.

Effects of selective 5-hydroxytryptamine-2 and nonselective 5-hydroxytryptamine antagonists on the differential-reinforcement-of-low-rate 72-second schedule.

  • G. MarekL. Seiden
  • Psychology, Biology
    The Journal of pharmacology and experimental therapeutics
  • 1988
The results suggest that the therapeutic effect of atypical antidepressants such as trazodone and mianserin may be related to selective antagonism of 5-HT2 receptors.

Selective 5-hydroxytryptamine2 antagonists have antidepressant-like effects on differential-reinforcement-of-low-rate 72-second schedule.

Selective antagonism of central 5-HT2 relative to 5- HT1 receptors results in antidepressant-like effects on the DRL 72-s schedule, and the specificity of the D RL 72-S schedule as a screen for antidepressant drugs was strengthened by the observation that the alpha-1 adrenergic antagonist, prazosin, did not increase the reinforcement rate despite significant decreases in the response rate.

The serotonin-1A receptor antagonist WAY-100635 modifies fluoxetine’s antidepressant-like profile on the differential reinforcement of low rates 72-s schedule in rats

The data demonstrate that the behavioral effects of fluoxetine are modified by 5-HT-1A receptor blockade, and this schedule is a behavioral screen selective and sensitive to antidepressant drugs.

A comparison of trazodone and fluoxetine: implications for a serotonergic mechanis of antidepressant action

The preclinical and clinical data suggest that trazodone acts as an antidepressant via antagonist action at 5-HT2/1C receptors, while fluoxetine likely acts as a antidepressant via inhibition of 5- HT uptake.

Effect of fluoxetine on extracellular 5-hydroxytryptamine in rat brain. Role of 5-HT autoreceptors.

Partial role of 5-HT2 and 5-HT3 receptors in the activity of antidepressants in the mouse forced swimming test.

The behavioral effects of sertraline, fluoxetine, and paroxetine differ on the differential-reinforcement-of-low-rate 72-second operant schedule in the rat

Results indicate that, although SSRIs are correctly identified as antidepressants by the DRL 72-s operant schedule, they may exert their effects in subtly different ways, as indicated by the differences observed to exist between the drugs.

A Novel Approach to the Identification of Psychiatric Drugs: Serotonin-Glutamate Interactions in the Prefrontal Cortex

It is suggested that elucidation of the specific receptors that suppress glutamate release induced by 5-HT2A receptor activation in the medial prefrontal cortex may lead to novel therapeutic targets for depression, such as metabotropic glutamate agonists which may not be efficacious in screening strategies primarily dependent on synaptic availability of monoaminergic neurotransmitters.

Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia.

Clozapine, at doses known to be effective in routine clinical settings, showed a D 2 occupancy clearly lower than that of typical antipsychotics, while risperidone and olanzapine at their usual clinical doses gave the same level of D2 occupancy as low-dose typical antippsychotics.
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