The importance of drug ionization for the action of calcium-antagonists and related compounds.

pK-Values of Ca-antagonists and related cardiodepressive drugs have been measured by means of potentiometric microtitration. The presumable active species for all compounds investigated is the protonated molecule except nifedipine. This drug must exert its action via the uncharged form. From these results it could be concluded that protonization of ionizable nitrogen is one molecular prerequisite for voltage- or frequency dependence of action. Drug ionization does not correlate with the negative inotropic potency of the compounds investigated.