Pharmacology of N-type Ca²⁺ channels distributed in cardiovascular system (Review)

Irregular functions in Ca²⁺ channels are intimately involved in many aspects of cardiovascular diseases. We can obtain a wide variety of L-type Ca²⁺ channel antagonists to treat hypertension and angina pectoris. Dihydropyridines (DHPs) have, first of all, been extensively developed due to their high selectivity for L-type Ca²⁺ channel and safety in pharmacological aspects. In contrast, many lines of evidence suggest that clinical efficacy of those DHPs are limited and undesirable effects are sometimes observed because of the specific distribution of L-type Ca²⁺ channels. As well as the L-type, peripherally distributed N-type Ca²⁺ channel plays a key role in cardiovascular regulation through autonomie nervous system. Recently, we developed a unique DHP derivative, cilnidipine (FRC8653) which has a dual antagonistic action on both L-type and N-type Ca²⁺ channels. Our recent studies with this DHP have made it clear that the N-type Ca²⁺ channel is also a new therapeutic target in cardiovascular diseases. We review the recent advances in pharmacology of the N-type Ca²⁺ channel and therapeutic implications of their antagonists.