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Thromb Haemost 1991; 65(04): 415-420
DOI: 10.1055/s-0038-1648163
Original Article
Schattauer GmbH Stuttgart

MCI–9042, a New Antiplatelet Agent Is a Selective S2-Serotonergic Receptor Antagonist

H Hara
Pharmaceuticals Laboratory Research Center, Mitsubishi Kasei Corporation, Yokohama, Japan
,
M Osakabe
Pharmaceuticals Laboratory Research Center, Mitsubishi Kasei Corporation, Yokohama, Japan
,
A Kitajima
Pharmaceuticals Laboratory Research Center, Mitsubishi Kasei Corporation, Yokohama, Japan
,
Y Tamao
Pharmaceuticals Laboratory Research Center, Mitsubishi Kasei Corporation, Yokohama, Japan
,
R Kikumoto
Pharmaceuticals Laboratory Research Center, Mitsubishi Kasei Corporation, Yokohama, Japan
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Publikationsverlauf

Received: 02. Juli 1990

Accepted after revision 26. November 1990

Publikationsdatum:
02. Juli 2018 (online)

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Summary

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 × 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 × 10–8 M, while Si 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.

 

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