Manzar Aarish, Sic Aleksandar, Banh Crystal, Knezevic Nebojsa Nick
Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL 60657, USA.
Department of Internal Medicine, Ziauddin Medical College, Karachi 75500, Pakistan.
Cells. 2025 Jul 20;14(14):1114. doi: 10.3390/cells14141114.
Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes. CCBs may also aid in managing primary aldosteronism and pheochromocytoma, particularly in patients with calcium signaling mutations. In pain medicine, α2δ ligands and selective blockers of N-type and T-type channels demonstrate efficacy in neuropathic and inflammatory pain. However, their broader use is limited by challenges in central nervous system (CNS) penetration, off-target effects, and heterogeneous trial outcomes. Future research should focus on pharmacogenetic stratification, novel delivery platforms, and combination strategies to optimize repurposing of CCBs across disciplines.
钙通道阻滞剂（CCBs）最初是为心血管适应症开发的，其在神经精神、内分泌和疼痛相关疾病中的治疗潜力已受到关注。在神经精神病学中，尼莫地平和伊拉地平这两种L型CCBs都具有情绪稳定和神经保护作用，可能对抑郁症、双相情感障碍和精神分裂症有益。在内分泌学中，维拉帕米这种非二氢吡啶L型阻滞剂与胰腺β细胞功能的保留以及糖尿病患者胰岛素依赖性的降低有关。CCBs还可能有助于治疗原发性醛固酮增多症和嗜铬细胞瘤，特别是在有钙信号突变的患者中。在疼痛医学中，α2δ配体以及N型和T型通道的选择性阻滞剂在神经性和炎性疼痛中显示出疗效。然而，它们更广泛的应用受到中枢神经系统（CNS）渗透、脱靶效应和试验结果异质性等挑战的限制。未来的研究应集中在药物遗传学分层、新型给药平台和联合策略上，以优化CCBs跨学科的重新利用。
