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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists.

At clinically relevant doses, selective serotonin (5-HT) reuptake inhibitors (SSRIs) and MAO inhibitors (MAOIs) increase the extracellular concentration of 5-HT in the midbrain raphé nuclei, thereby activating inhibitory somatodendritic 5-HT1A autoreceptors. Consequently, the firing activity of 5-HT neurons is reduced and the enhancement of extracellular 5-HT concentration in forebrain is dampened. Overriding this feedback by using antagonists of 5-HT1A autoreceptors permits SSRIs to produce a marked increase of extracellular 5-HT in the forebrain. Hence, combined treatment with an SSRI and a 5-HT1A antagonist increases the extracellular concentration of 5-HT more so than the former drug alone. The treatment of patients with major depression using an SSRI and pindolol, a 5-HT1A/ beta-adrenoceptor antagonist, markedly reduced the latency of the antidepressant response in previously untreated patients and induced a rapid improvement in treatment-resistant patients.[1]

References

  1. Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Artigas, F., Romero, L., de Montigny, C., Blier, P. Trends Neurosci. (1996) [Pubmed]
 
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