P-1086 - Impact of antipsychotics on thromboxane production in-vitro

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• 作者：H. Himmerich ; L. Schmidt ; J. Schö ; nherr ; K. Bauer ; U. Sack ; B. Niescher ; J. Thiery ; S. Becker ; U. Ceglarek
• 刊名：European Psychiatry
• 出版年：2012
• 出版时间：2012
• 年：2012
• 卷：27
• 期：supp_S1
• 页码：1
• 全文大小：66 K

文摘

Introduction

Thromboxane (TX) A2 and the activation of its receptor have been shown to modulate vasoconstriction, platelet aggregation, but also dopaminergic and serotonergic signaling.

As dopaminergic and serotonergic systems play a crucial role in the pathophysiology of schizophrenia and as these systems are main targets of antipsychotics, we hypothesized that antipsychotics might also influence TXA2 production.

Methods

We measured levels of TXB2, the metabolite of the very unstable molecule TXA2, in the stimulated blood of 10 healthy female subjects in a whole blood assay using the toxic shock syndrome toxin-1 (TSST-1) and the monoclonal antibody against the surface antigen CD3 combined with the protein CD40 (OKT3/CD40) as stimulants. Blood was either supplemented with antipsychotics (chlorpromazine, clozapine, and its metabolite N-desmethylclozapine with four different concentrations each) or not.

Results

Under TSST-1 as well as OKT3/CD40 stimulation, mean TXB2 concentrations were significantly (p < 0.05) decreased by clozapine over all of the applied concentrations. N-desmethylclozapine led to a decrease in TXB2 levels under TSST-1 stimulation only. Chlorpromazine did not show any significant influence on TXB2 production.

Conclusions

Clozapine might, complementary to serotonin and dopamine receptor binding, act on the dopaminergic and serotonergic system via a modulation of TXA2 production. Additionally, side effects of clozapine such as orthostatic hypotension may be a result of the reported TXA2 changes.