Dotarizine

Dotarizine is a broad spectrum Ca²⁺ antagonist and calcium channel protein inhibitor which blocks calcium uptake, [Ca²⁺]i rise and secretion via blockade of calcium channels. In addition, dotarizine selectively binds to vascular 5-HT receptors, blocking Ca²⁺ activated Cl ^-channels. Dotarizine is a piperazine derivative structurally related to flunarizine, which accounts for the similar function of the two compounds. Furthermore, flunarizine is a less selective antagonist than dotarizine towards SR (5-HT receptors). Alternate studies indicate that dotarizine can inhibit cell death in bovine adrenal medullary chromaffin cells by decreasing cytosolic Ba²⁺ concentration via Ca²⁺ channel blockade.