Premium
Molecular Pharmacological Aspects of Antiarrhythmic Activity, II 1 ): Interaction of Class I Compounds with Calmodulin
Author(s) -
Mannhold Raimund,
Voigt Werner,
Bast Aalt,
Timmerman Hendrik
Publication year - 1990
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19903230809
Subject(s) - lipophilicity , potency , calmodulin , chemistry , propafenone , phosphodiesterase , stereochemistry , inhibitory postsynaptic potential , pharmacology , in vitro , biochemistry , enzyme , medicine , biology , endocrinology , atrial fibrillation
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, R M ) and two calculative (Σf, C log P) procedures. Five antiarrhythmics (asocainol, aprindine, lorcainide, propafenone, and ethmozine) exhibit IC 50 values < 250 μM 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.