A molecular graphics study on structure-action relationships of calcium-antagonistic and agonistic...

Based on force field and quantum chemical calculations a hypothesis on the molecular mechanism of Ca channel-modulating 1,4-dihydropyridines (DHPs) has been developed. A careful investigation of the molecular electrostatic fields of the compounds led to the discovery of a unique area of the molecular potentials where Ca agonists and antagonists possess potentials with opposite sign. It is further demonstrated that the molecular potential of a simple receptor site model is reduced by interaction with Ca channel-activating DHPs and on the contrary increased by Ca channel-blocking DHPs. It is concluded that these effects could be the basis for opposite actions of 1,4-dihydropyridine enantiomers at the potential-dependent Ca channels.