Effect of sarpogrelate, a 5-HT(2A) antagonist, on platelet aggregation in patients with ischemic stroke: clinical-pharmacological dose-response study

Cerebrovasc Dis. 2007;24(2-3):264-70. doi: 10.1159/000105135. Epub 2007 Jul 4.

Abstract

Background and purpose: It is widely accepted that antiplatelet therapy is effective for secondary prevention of atherosclerotic vascular diseases. We performed a double-blind, controlled clinical-pharmacological study to investigate the antiplatelet efficacy of sarpogrelate, a selective 5-hydroxytryptamine (5-HT(2A)) receptor antagonist, in patients with ischemic stroke, using a new assessment system employing combinations of 5-HT and epinephrine as agonists.

Methods: Forty-seven patients with ischemic stroke were randomly assigned to three groups: 15 patients received 25 mg sarpogrelate (group L), 16 patients received 50 mg (group M), and 15 patients received 100 mg (group H) orally, three times daily for 7 days. The effect was expressed as maximum intensity of platelet aggregation on the last day of medication. Two combinations of agonists, 0.5 micromol/l 5-HT plus 3 micromol/l epinephrine, and 1 micromol/l 5-HT plus 3 micromol/l epinephrine, were used to induce platelet aggregation.

Results: With both combinations of agonists, sarpogrelate treatment inhibited platelet aggregation dose-dependently (p < 0.025, Jonckheere test). In multiple-group comparison, the effect in group H was greater than that in group L or M (p < 0.025, Wilcoxon rank-sum test).

Conclusion: Sarpogrelate treatment inhibited platelet aggregation dose-dependently in patients with ischemic stroke, as judged by a new assessment system employing combinations of 5-HT and epinephrine as agonists.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Brain Ischemia / blood
  • Brain Ischemia / complications*
  • Brain Ischemia / drug therapy
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Epinephrine / metabolism
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests / methods
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Serotonin / metabolism
  • Serotonin 5-HT2 Receptor Antagonists*
  • Serotonin Antagonists / administration & dosage
  • Serotonin Antagonists / adverse effects
  • Serotonin Antagonists / therapeutic use*
  • Stroke / blood
  • Stroke / drug therapy*
  • Stroke / etiology
  • Succinates / administration & dosage
  • Succinates / adverse effects
  • Succinates / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Receptor, Serotonin, 5-HT2A
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Antagonists
  • Succinates
  • sarpogrelate
  • Serotonin
  • Epinephrine