Molecular orbital index-activity relationship between atrial antiarrhythmic activity and disopyramide derivatives.
TENGK. LIN, YIEW. CHIEN, HITENDRAB. DESAI, PETERK. YONAN · Chemical and Pharmaceutical Bulletin · 1976
A model has been proposed to explain and determine biological response to antiarrhythmic compounds. A series of compounds was administered to mongrel dogs and tested for their ability to correct the induced arrhythmias. This drug response is shown to be a function of lipophilicity, IR-absorption and electrostatic interaction. Frontier electron density is shown as a good parameter in the comparison of electrostatic interaction between different molecules and is significantly correlated with biological activity. This parameter is shown as a possible explanation for the observation that compounds with a high value of lipophilicity and low value of electrostatic factor may show good ventricular antiarrhythmic activity but fail to show atrial antiarrythmic activity.