Effects of sarpogrelate, a 5-hydroxytriptamine 2A receptor antagonist on endotoxin shock in rats

Introduction

It is known that 5-hydroxytriptamine (5-HT)2A receptors have some roles in vascular constriction, platelet aggregation, and superoxide production by neutrophils. 5-HT2A receptor antagonists are therefore expected to be effective for sepsis. The present study was performed to investigate the effects of sarpogrelate, a 5-HT2A receptor antagonist on endotoxin shock in rats.

Methods

Male Sprague–Dawley rats were anesthetized with halothane. Catheters were inserted into the femoral artery and the femoral vein. Sarpogrelate 0, 3, or 10 mg/kg dissolved in 0.5 ml clear water was administered intravenously followed by 10 mg/kg endotoxin 5 min later. The blood pressure (BP), pulse rate (PR), and survival rate were monitored for 4 hours in 20 rats at each dose. Arterial blood was drawn before, 2 and 4 hours after endotoxin administration to measure IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) (another eight rats at each dose).

Results

The decreases in BP and PR were significantly bigger in the 0 mg/kg group than the 3 mg/kg and 10 mg/kg groups. Survival rates were significantly lower in the 0 mg/kg group than the other two groups. IL-1β at 4 hours was significantly higher in the 0 mg/kg group than the other two groups. TNF-α at 2 hours was significantly lower in the 3 mg/kg group than the other two groups. The data at 4 hours are presented in Table 1 as the mean ± standard deviation.

Table 1

Discussion

Pretreatment with sarpogrelate inhibited the decrease in BP and PR and decreased mortality. Cytokine levels had big variations, but sarpogrelate had a tendency to decrease IL-1β, IL-6, IL-8, and TNF-α, and to increase IL-10. Sarpogrelate 3 mg/kg was more effective than 10 mg/kg; probably 10 mg/kg decreased BP more than 3 mg/kg. In the preliminary study, BP was dose-dependently decreased by sarpogrelate and 30 mg/kg killed animals. Therefore, sarpogrelate 3 mg/kg might be the choice.

Conclusion

Intravenous sarpogrelate might be effective for endotoxin shock.