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The Role of GABA-A Receptor in the Synergism Between SSRI and Antipsychotic in Schizophrenia; Implications for Antipsychotic Modes of Actions

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Abstract:

Antipsychotics, old and new varieties, are effective against positive symptoms such as hallucination and delusions, but are often of limited value in treating core features of schizophrenia particularly negative symptoms. Developments of new drugs based on current dogmas have produced similar drugs with no breakthroughs in effectiveness. New knowledge as to which mechanisms are responsible for symptom productions and treatment is needed.

There is evidence that response may improve when antipsychotics are augmented with selective serotonin reuptake inhibitor (SSRI). This augmenting effect cannot be explained by summating pharmacological effects of the individual drugs. In a series of laboratory and clinical studies, we identified unique biochemical effects of the SSRI-Antipsychotic combination, different from each individual drug and suggested that some of these may mediate the clinical effect. In this paper, we review these studies and propose that modulation of the gamma-aminobutyric acid (GABA)-A receptor and its regulating system is the mechanism by which SSRI antipsychotic synergism exerts its clinical efficacy.

Keywords: GABA-A receptor; Schizophrenia; antipsychotic drugs; negative symptoms; selective serotonin reuptake inhibitors

Document Type: Research Article

Publication date: January 1, 2013

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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