Both L-type (Ca_V1) and T-type (Ca_V3) voltage-gated Ca²⁺ channels are large (~0.5 MDa), transmembrane proteins which control the cellular influx of Ca²⁺ in response to electrical stimuli. While Ca_V1s require a strong depolarization (~+40 mV) to perform, a much weaker pulse (~-40 mV) is sufficient to activate Ca_V3s¹.

Ca²⁺ channel blockers (CCBs) are a diverse class of pharmaceutical agents, usually targeting L-type channels, of which dihydropyridines (DHPs) constitute a major subgroup^2,3. Inhibitors of Ca²⁺-mediated smooth muscle contractions, CCBs produce vasodilation, thus therapeutically managing hypertension and coronary heart disease².

An antagonist of both Ca_V1 (all subtypes) and Ca_V3 (α_1G and α_1H subtypes)⁴, azelnidipine (AZL) is a DHP derivate⁵ known to target Ca_Vs with an IC₅₀ of 3 nM⁶. Its long-lasting interaction at multiple binding sites of L-type Ca²⁺ channels renders it resistant to S(-)-Bay K8644 (Ca_V1 channel agonist) activating effects, otherwise shown to counteract nifedipine-induced inhibition⁶; AZL thus confers significantly prolonged cardioactive time⁷. Its reduced side effects and improved cardiovagal baroreflex sensitivity (BRS) when clinically administered make ALZ's therapeutic benefits superior to that of the potent antihypertensive, amlodipine⁸. Additionally, ALZ possesses hydragogue, heart-protective, kidney-protective, and anti-arteriosclerosis capabilities⁷.