Two voltage-gated calcium channel subtypes—Ca_V1.2 and Ca_V1.3—underlie the major L-type Ca²⁺ currents in the mammalian central nervous system. Owing to their high sequence homology, the two channel subtypes share similar pharmacological properties, and at high doses classic calcium channel blockers, such as dihydropyridines, phenylalkylamines and benzothiazepines, do not discriminate between the two channel subtypes. Recent progress in treating Parkinson’s disease (PD) was marked by the discovery of synthetic compound 8, which was reported to be a highly selective inhibitor of the Ca_V1.3 L-type calcium channels (LTCC). However, despite a previously reported IC₅₀ of ~24 μM, in our hands inhibition of the full-length Ca_V1.3₄₂ by compound 8 at 50 μM reaches a maximum of 45%. Moreover, we find that the selectivity of compound 8 towards Ca_V1.3 relative to Ca_V1.2_B15 channels is greatly influenced by the β-subunit type and its splice isoform variants.