Department of Ophthalmology, University of Tokyo Graduate School of Medicine, 7-3-1, Hongo, Bunkyo-ku, 113-8655 Tokyo, Japan.
Prog Retin Eye Res. 2011 Jan;30(1):54-71. doi: 10.1016/j.preteyeres.2010.09.002. Epub 2010 Oct 8.
Calcium channel blockers (CCBs), which alter the intracellular calcium concentration by modifying calcium flux across cell membranes and affect various intracellular signaling processes, have been long and widely used to treat essential hypertension and certain types of cardiac diseases such as angina pectoris. Among five subtypes of calcium channels, only specific agents for L-type calcium channels have been used as therapeutics. Animal experiments have indicated that topical application of CCBs, especially verapamil, caused significant intraocular pressure (IOP) reductions, while ocular hypotensive effects in humans were not substantial. Although the results obtained for nifedipine and nimodipine were not always consistent, CCBs generally dilate isolated ocular vessels and increase ocular blood flow in experimental animals, normal humans, and patients with open-angle glaucoma (OAG). Several single-centered, hospital-based, prospective studies have suggested that nimodipine, brovincamine, and nilvadipine had beneficial effects on visual function not only in normal humans but also in patients with OAG, while the results of population-based and case-controlled studies were not always consistent with those obtained in hospital-based studies. In vitro studies showed that CCBs exerted neuroprotective effects on neurons undergoing apoptosis and necrosis. Although the neuroprotective effects of CCBs have been well documented in experimental cerebral ischemia models, no controlled studies have shown the clinical efficacy of CCBs in stroke or cerebral ischemia. Neuroprotective effects also were documented in retinal ganglion cells and photoreceptors in experimental animals. Some ophthalmic beta-adrenoceptor antagonists, especially betaxolol, interact with L-type calcium channels and show calcium channel-blocking activity, which may be partly responsible for the neuroprotective effects of these drugs reported in experimental animals. Based on the reported findings of CCBs and that the results of clinical studies in acute cerebral ischemia may not be directly applicable to a chronic neurodegenerative ocular disorder, such as OAG, CCBs deserve future study to investigate strategies that are additive or synergetic to ocular hypotensive therapy for OAG, especially in patients with lower IOP.
钙通道阻滞剂（CCBs）通过改变细胞膜上钙的流动来改变细胞内钙浓度，影响各种细胞内信号转导过程，长期以来一直被广泛用于治疗原发性高血压和某些类型的心脏病，如心绞痛。在五种钙通道亚型中，只有特定的 L 型钙通道药物被用作治疗药物。动物实验表明，CCBs ，特别是维拉帕米，局部应用可显著降低眼内压（IOP），而在人类中，其降低眼内压的作用并不显著。虽然硝苯地平和尼莫地平的结果并不总是一致，但 CCBs 通常可扩张离体眼血管，并增加实验动物、正常人和开角型青光眼（OAG）患者的眼血流。几项单中心、基于医院的前瞻性研究表明，尼莫地平、溴苯辛和尼伐地平不仅对正常人群，而且对 OAG 患者的视力均有有益作用，而基于人群和病例对照的研究结果并不总是与基于医院的研究结果一致。体外研究表明，CCBs 对凋亡和坏死神经元具有神经保护作用。虽然 CCBs 在实验性脑缺血模型中已被证明具有神经保护作用，但没有对照研究表明 CCBs 在中风或脑缺血中的临床疗效。在实验动物中，视网膜神经节细胞和光感受器也具有神经保护作用。一些眼科β-肾上腺素受体拮抗剂，特别是倍他洛尔，与 L 型钙通道相互作用并具有钙通道阻滞活性，这可能是这些药物在实验动物中报告的神经保护作用的部分原因。基于 CCBs 的报告结果以及急性脑缺血的临床研究结果可能不适用于慢性神经退行性眼病，如 OAG，因此 CCBs 值得进一步研究，以探索对 OAG 降压治疗具有附加或协同作用的策略，特别是在 IOP 较低的患者中。
