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Thromb Haemost 1991; 66(04): 484-488
DOI: 10.1055/s-0038-1646443
Review Article
Schattauer GmbH Stuttgart

Antithrombotic Effect of MCI-9042, a New Antiplatelet Agent on Experimental Thrombosis Models

H Hara
The Pharmaceuticals Laboratory, Research Center, Mitsubishi Kasei Corporation, Yokohama, Japan
,
A Kitajima
The Pharmaceuticals Laboratory, Research Center, Mitsubishi Kasei Corporation, Yokohama, Japan
,
H Shimada
The Pharmaceuticals Laboratory, Research Center, Mitsubishi Kasei Corporation, Yokohama, Japan
,
Y Tamao
The Pharmaceuticals Laboratory, Research Center, Mitsubishi Kasei Corporation, Yokohama, Japan
› Author Affiliations
Further Information

Publication History

Received 02 July 1990

Accepted 12 April 1991

Publication Date:
25 July 2018 (online)

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Summary

The antithrombotic effect of MCI-9042, (±)-2-(dimethylamino)-1-[[o-(m-methoxyphenethyl)phenoxy] methyl] ethyl hydrogen succinate hydrochloride was investigated in three different experimental thrombosis models in animals. Simultaneous injection of serotonin and collagen into the tail vein in mice induced acute pulmonary thromboembolic death. MCI-9042 reduced the mortality in a dose dependent manner and its ED50 value was 1.9 mg/kg po. Ticlopidine (TCP) which is a positive reference compound as an antithrombotic drug reduced the mortality at doses of 10 mg/kg po and above. Cyproheptadine (CPH) and ketanserin (KTS) which are S2-serotonergic antagonists were also effective on the reduction of mortality. In mesenteric arterial thrombosis induced by electric stimulation in mice, MCI-9042 prolonged the occlusion time resulted from platelet thrombus formation (PD50: 23 mg/kg po). CPH and KTS prolonged the occlusion time as potent as MCI-9042, but TCP prolonged the occlusion time only at the high doses of 100 mg/kg po and above. In experimental arterial thrombosis which generated in implanted polyethylene tubing, MCI-9042 reduced the incidence of thrombus formation in the tubing and its ED50 value was 18 mg/kg po. TCP was also effective in this model with an ED50 of 170 mg/kg po. The present results lead to the consideration that serotonin plays a more important role in thrombus formation than that conjectured formerly, and suggest that MCI-9042 becomes a new kind of antithrombotic drug with S2-serotonergic receptor antagonism.

 

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