Interaction of calcium channel antagonists with calcium: structural studies on nicardipine and its Ca2+ complex.

Conformational features of nicardipine in acetonitrile, in the absence and presence of Ca 2+ , were investigated by one-dimensional NMR and difference absorption spectroscopy techniques. The data show that in acetonitrile solution the antiperiplanar form of nicardipine is domi- nant. The addition of Ca 2+ to the drug solution caused marked changes in the difference absorbance spectra in the 200-400 nm region and in many of its 1 H and 13 C NMR resonances. The changes were most signi- ficant up to a ratio of 0.5 Ca 2+ :drug. Analysis of the binding data showed the predominant species to be a 2:1 drug:Ca 2+ «sandwich» complex with an estimated dissociation constant of 100 μM at 25 o C