Effect of three calcium antagonists on platelet secretion and metabolism

Three compounds, 8-(N,N-diethylamino-octyl 3,4,5-trimethoxybenzoate, HCl (TMB-8), 2-propyl-3-dimethylamino-5,6-methylenedioxyindene HCl (2-PIA), and chlortetracycline, were investigated to determine whether their effects on washed human platelets were compatible with a suggested role as calcium antagonists. TMB-8 had little effect on levels of metabolic ATP and IMP, whereas chlortetracycline caused a decrease in metabolic ATP and an increase in IMP; both compounds inhibited thrombin-induced secretion and changed the platelets to spheres. At concentrations up to 0.5 mM, 2-PIA caused a decrease in ATP and an increase in IMP, an induction of secretion, and a centralization of electron-dense material in the platelets, all changes which suggest induction of secretion. The ultrastructural, functional and metabolic effects of TMB-8 and the type of interference by the drug with the effects of thrombin and 2-PIA on the same variables suggest that TMB-8 is mainly a membrane-active drug. Chlortetracycline on the other hand caused changes in platelet metabolism, ultrastructure, and function which, at least partly, indicate an effect on intracellular mechanisms. Both TMB-8 and 2-PIA, and to lesser degree chlortetracycline, caused loss of cytoplasmic nucleotides from the platelets.