Selectivities of dihydropyridine derivatives in blocking Ca2+ channel subtypes expressed in Xenopus oocytes

Some dihydropyridines (DHPs), such as amlodipine and cilnidipine, have been shown to block not only L-type but also N-type Ca2+ channels; therefore, D HPs are no longer considered as L-type-specific Ca2+ channel blockers. Howe ver, selectivity of DHPs for Ca2+ channel subtypes including N-, P/Q-, and R-types are poorly understood. To address this issue at the molecular level , blocking effects of 10 DHPs (nifedipine, nilvadipine, barnidipine, nimodi pine, nitrendipine, amlodipine, nicardipine, benidipine, felodipine, and ci lnidipine) on four subtypes of Ca2+ channels (L-, N-, P/Q-, and R-types) we re investigated in the Xenopus oocyte expression system with the use of the two-microelectrode voltage-clamp technique. L-type Ca2+ channels expressed as alpha(1C)alpha(2)beta(1a) combination were profoundly blocked by all DH Ps examined, whereas blocking actions of these DHPs on R-type (alpha(1E)alp ha(2)beta(1a)) channels were equally weak. In contrast, 5 of the 10 DHPs (a mlodipine, benidipine, cilnidipine, nicardipine, and barnidipine) significa ntly blocked N-type (alpha(1B)alpha(2)beta(1a)) and P/Q-type (alpha(1A)alph a(2)beta(1a)) Ca2+ channels. These selectivities of DHPs in blocking Ca2+ c hannel subtypes would provide useful pharmacological and clinical informati on on the mode of action of the drugs including side effects and adverse ef fects.