Effects of Diltiazem on Platelet Functions

Abstract

An investigation was made of the effect of Diltiazem, a drug used for ischemic heart diseases, on platelet function and the following results have been obtained:
1. Diltiazem suppressed platelet adhesiveness and aggregation in vitro at concentrations greater than 100 μg/ml, but in vivo this effect was not pronounced at the normal doses investigated here. It was thought that this discrepancy was due to the difference in concentration of the drug in blood.
2. Doses of Diltiazem greater than 100 μg/ml were capable of suppressing aggregation even with the addition of various inducers, including ADP, collagen, adrenalin, thrombin, bovine fibrinogen, arachidonic acid and CaCl₂.
3. The suppression of aggregation by this drug was due to its blocking action on phosphodiesterase, which caused an increase in cyclic AMP.
4. There was a discrepancy between the concentration of this drug needed for a suppression of Aa-induced platelet aggregation and a decrease of malondialdehyde synthesis. Aa aggregation suppression was not caused solely by the inhibition of the production of endoperoxide, but rather through the action of cyclic AMP.
5. Diltiazem had no effect on platelet aggregation through extracellular Ca concentrations.