MCI-9042, a new antiplatelet agent is a selective S2-serotonergic receptor antagonist

Thromb Haemost. 1991 Apr 8;65(4):415-20.

Abstract

MCI-9042, (+/-)-1-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]-3- (dimethylamino)-2-propyl hydrogen succinate hydrochloride inhibited platelet aggregation induced by collagen and secondary aggregation by ADP or epinephrine at 10(-6) M level in platelets of various species. The antiplatelet effect of MCI-9042 was potentiated in aggregation induced by a combination of serotonin with collagen. IC50 value of human platelet aggregation by the serotonin plus collagen was 1.0 x 10(-7) M. MCI-9042 inhibited serotonin release accompanied with collagen-induced platelet aggregation, while it did not affect serotonin uptake into platelet. MCI-9042 also potently inhibited the S2-serotonergic receptor-mediated contraction of rat caudal artery by serotonin in a competitive manner with a Ki value of 1.79 x 10(-8) M, while S1 receptor- or adrenergic receptor-mediated vasoconstriction was inhibited more weakly. Platelet adhesiveness, c-AMP level in platelets and the conversion of arachidonic acid to thromboxane A2 were not influenced by MCI-9042. These results suggest that MCI-9042 is a selective S2-serotonergic receptor antagonist, exhibiting the inhibition of S2-serotonergic potentiated platelet aggregation and the suppression of blood vessel constriction mediated by S2-serotonergic receptor.

MeSH terms

  • Animals
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Humans
  • In Vitro Techniques
  • Muscle, Smooth, Vascular / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Rabbits
  • Rats
  • Receptors, Serotonin / drug effects*
  • Succinates / pharmacology*
  • Vasoconstriction / drug effects

Substances

  • Platelet Aggregation Inhibitors
  • Receptors, Serotonin
  • Succinates
  • sarpogrelate