Molecular pharmacological aspects of antiarrhythmic activity, II: Interaction of class I compounds with calmodulin

We have tested the calmodulin (CaM) inhibitory potency of class I antiarrhythmics in the phosphodiesterase (PDE) assay. The lipophilicity of the test compounds has been quantified by two experimental (log P, RM) and two calculative (sigma f, C log P) procedures. Five antiarrhythmics (asocainol, aprindine, lorcainide, propafenone, and ethmozine) exhibit IC50 values less than 250 microM for the inhibition of the CaM-stimulated PDE activity. Lipophilicity seems to be a prime, but not the sole descriptor of CaM inhibitory potency. The functional means of CaM inhibition by the test compounds for their antiarrhythmic properties remains to be clarified in further investigations.