Calcium channel agonist and antagonist effects of the stereoisomers of the dihydropyridine 202-791

The effects of the pure stereoisomers of the novel dihydropyridine 202-791 on voltage sensitive calcium channels in nerve and cardiac muscle were examined. The (-)-isomer blocked depolarization-induced uptake of ⁴⁵Ca²⁺ into NG108-15 neuroblastoma x glioma cells, blocked the depolarization-induced release of [³H]-norepinephrine from PC12 cells and reduced the Vmax of the slow response action potential recorded from guinea pig papillary muscle. In contrast, the (+)-isomer enhanced these same processes. In papillary muscle, greater enhancement of the slow responses was observed at lower stimulation frequencies. Thus, the (-) and (+) stereoisomers of 202-791 can be shown to be calcium channel antagonist and agonist respectively.