Effects of McN-6186 on voltage-dependent Ca⁺⁺ channels in heart and pituitary cells

McN-6186 (N-[2-(3,5-dimethoxyphenyl)ethyl]-5-methoxy-α-methyl-2- (phenylethynyl) benzeneethanamine hydrochloride is a compound structurally distinct from other Ca⁺⁺ channels ligands. McN-6186 showed some stimulation of 1,4-dihydropyridine-sensitive Ca⁺⁺ uptake in neonatal rat ventricular cells at concentrations of 1 and 3 nM. At higher concentrations McN-6186 inhibited this uptake in rat ventricular cells at concentrations approximately 100-fold less than those needed to block the corresponding Ca⁺⁺ uptake in rat anterior pituitary (GH₃) cells. McN-6186 (2 μM) inhibited L-type Ca⁺⁺ channel current in neonatal rat ventricular cells in a voltage-dependent manner while having little or no effect on this current in GH₃ cells. In some ventricular cells tested, the T-type Ca⁺⁺ current was also blocked by 2 μM McN-6186. McN-6186 inhibited (+)-[³H]PN200-110 binding in rat cardiac membranes with an IC₅₀ value of 1.45 x 10^-7 M and a shallow Hill slope (n(H) = 0.42). It is concluded that McN-6186 blocks L-type Ca⁺⁺ channels in heart cells preferentially to those found in GH₃ cells. Furthermore, McN-6186 may have other sites and mechanisms of action in addition to L-type Ca⁺⁺ channel blockade.