Aldosterone-producing adenomas (APAs) vary in phenotype and genotype. Zona glomerulosa (ZG)-like APAs frequently have mutations of an L-type calcium channel (LTCC) Ca V 1.3. Using a novel antagonist of Ca V 1.3, compound 8, we investigated the role of Ca V 1.3 on steroidogenesis in the human adrenocortical cell line, H295R, and in primary human adrenal cells. This investigational drug was compared with the common antihypertensive drug nifedipine, which has 4.5-fold selectivity for the vascular LTCC, Ca V 1.2, over Ca V 1.3. In H295R cells transfected with wild-type or mutant Ca V 1.3 channels, the latter produced more aldosterone than wild-type, which was ameliorated by 100 1/4M of compound 8. In primary adrenal and non-transfected H295R cells, compound 8 decreased aldosterone production similar to high concentration of nifedipine (100 1/4M). Selective Ca V 1.3 blockade may offer a novel way of treating primary hyperaldosteronism, which avoids the vascular side effects of Ca V 1.2-blockade, and provides targeted treatment for ZG-like APAs with mutations of Ca V 1.3.