Striessnig Jörg, Ortner Nadine J, Pinggera Alexandra
Department of Pharmacology and Toxicology, Institute of Pharmacy, Center for Molecular Biosciences, University of Innsbruck, A-6020 Innsbruck, Austria.
Curr Mol Pharmacol. 2015;8(2):110-22. doi: 10.2174/1874467208666150507105845.
Inhibition of voltage-gated L-type calcium channels by organic calcium channel blockers is a well-established pharmacodynamic concept for the treatment of hypertension and cardiac ischemia. Since decades these antihypertensives (such as the dihydropyridines amlodipine, felodipine or nifedipine) belong to the most widely prescribed drugs world-wide. Their tolerability is excellent because at therapeutic doses their pharmacological effects in humans are limited to the cardiovascular system. During the last years substantial progress has been made to reveal the physiological role of different L-type calcium channel isoforms in many other tissues, including the brain, endocrine and sensory cells. Moreover, there is accumulating evidence about their involvement in various human diseases, such as Parkinson's disease, neuropsychiatric disorders and hyperaldosteronism. In this review we discuss the pathogenetic role of L-type calcium channels, potential new indications for existing or isoform-selective compounds and strategies to minimize potential side effects.
有机钙通道阻滞剂对电压门控L型钙通道的抑制作用是治疗高血压和心脏缺血的一个成熟的药效学概念。几十年来，这些抗高血压药物（如二氢吡啶类的氨氯地平、非洛地平或硝苯地平）一直是全球处方量最大的药物之一。它们的耐受性极佳，因为在治疗剂量下，其对人体的药理作用仅限于心血管系统。在过去几年中，人们在揭示不同L型钙通道亚型在包括脑、内分泌和感觉细胞在内的许多其他组织中的生理作用方面取得了重大进展。此外，越来越多的证据表明它们与各种人类疾病有关，如帕金森病、神经精神疾病和醛固酮增多症。在这篇综述中，我们讨论了L型钙通道的致病作用、现有或亚型选择性化合物的潜在新适应症以及将潜在副作用降至最低的策略。
