Formamidine-mediated inhibition of rat platelet aggregation.
The formamidine pesticide chlordimeform (CDF) was a strong inhibitor of aggregation of rat platelets induced by collagen and arachidonic acid and was a weak inhibitor of that induced by ADP. With the exception of 4-chloro-o-formotoluidide which was an inhibitor of arachidonic acid-induced aggregation only, the CDF metabolites were without discernible effect on aggregation induced by these agents. Amitraz, another formamidine pesticide, inhibited arachidonic acid-induced aggregation but was without effect on that induced by collagen or ADP. Inhibition of collagen- and/or arachidonic acid-induced aggregation by formamidines was concentration-dependent. Although platelets underwent shape change, primary aggregation was markedly inhibited, and secondary aggregation was abolished in some cases. CDF, its two N-desmethyl metabolites, and octopamine, but not amitraz, caused significantly elevated levels of cyclic AMP in platelet rich plasma as compared to controls; however, this effect did not fully account for the action of formamidines on aggregation.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002742:Chlorphenamidine / Q000378:metabolism / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D008297:Male; D009655:Octopamine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014052:Toluidines / Q000494:pharmacology*
D000578:Amidines; D001095:Arachidonic Acids; D014052:Toluidines; D009655:Octopamine; C006996:4'-chloro-2-formotoluidide; D016718:Arachidonic Acid; C014983:amitraz; D000244:Adenosine Diphosphate; D003094:Collagen; C028435:2-octopamine; D000242:Cyclic AMP; D002742:Chlorphenamidine