The antithrombogenic in vivo effects of calcium channel blockers in experimental thrombosis in mice.
A new model of thrombotic challenge, well suited for screening agents and which acts primarily against platelet thromboembolism, has been used to test the in vivo anti-platelet effects of four calcium channel blockers (CCB). An i.v. injection of a mixture of collagen plus epinephrine (15 micrograms and 1.8 micrograms/mouse, respectively) was given to male mice. 94% control mice died or remained paralyzed for more than 15 minutes. The dihydropyridine agents, CRE-223 and Nifedipine, were highly protective against experimental thrombosis, whereas Verapamil had a weaker and much shorter effect and, on the other hand, Diltiazem had no protective effect over a range of doses. The activity on both dihydropyridines lasted for seven hours or even longer.
Ortega
M P
MP
Departamento de Investigación, Alter, S.A., Mateo Inurria, Madrid, Spain.
Sunkel
C
C
Priego
J G
JG
Statkow
P R
PR
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003094:Collagen / Q000008:administration & dosage / Q000009:adverse effects; D004095:Dihydropyridines / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009543:Nifedipine / Q000494:pharmacology; D013927:Thrombosis / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D003094:Collagen; C053883:CRE 223; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D004837:Epinephrine