Platelet responsiveness to yohimbine hydrochloride and MRS2179 in the context of the interaction between collagen and epinephrine in acute coronary syndrome

Blood Cells Mol Dis. 2009 Jul-Aug;43(1):105-10. doi: 10.1016/j.bcmd.2009.02.002. Epub 2009 Mar 9.

Abstract

Acute coronary syndrome (ACS) covers a spectrum of clinical conditions ranging from unstable angina, Non-ST segment elevation myocardial infarction (NSTEMI), or ST segment elevation myocardial infarction (STEMI). This study encompasses patients with acute coronary syndrome, who were receiving the dual antiplatelet therapy of aspirin and clopidogrel. The focus of the study was to gain insight into the role of selective P2Y1 antagonism using MRS2179 in such cases as well as its effects, if any, on collagen-epinephrine interaction. All the cases showed greater potency of inhibition of the interaction when yohimbine hydrochloride (YH), a blocker of alpha2A-adrenoreceptor, was used compared to MRS2179, a P2Y1 antagonist, although there was variability in responsiveness to the antiplatelet drugs. These findings indicate that alpha2A-adrenoreceptors of platelets in this group play a major role in precipitating the interactive effect of collagen and epinephrine. The dose-response effect as studied by platelet aggregometry showed that the required molar concentration to block the interactive effect in the case of YH was less than that of MRS2179. Hence, it is postulated that although there may be an impairment of collagen-induced aggregation by MRS2179, the interactive effect of collagen-epinephrine may not be impaired by MRS2179 as efficaciously as YH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Adenosine Diphosphate / analogs & derivatives*
  • Adenosine Diphosphate / pharmacology
  • Adenosine Diphosphate / therapeutic use
  • Adrenergic alpha-Antagonists / pharmacology
  • Adrenergic alpha-Antagonists / therapeutic use*
  • Aged
  • Aspirin / therapeutic use
  • Blood Platelets / drug effects*
  • Clopidogrel
  • Collagen / metabolism
  • Drug Interactions
  • Epinephrine / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use
  • Purinergic P2 Receptor Antagonists*
  • Receptors, Purinergic P2Y1
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Yohimbine / pharmacology
  • Yohimbine / therapeutic use*

Substances

  • Adrenergic alpha-Antagonists
  • N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate
  • P2RY1 protein, human
  • Platelet Aggregation Inhibitors
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2Y1
  • Yohimbine
  • Adenosine Diphosphate
  • Collagen
  • Clopidogrel
  • Ticlopidine
  • Aspirin
  • Epinephrine