Popović Natalija, Morales-Delgado Nicanor, Vidal Mena David, Alonso Antonia, Pascual Martínez María, Caballero Bleda María, Popović Miroljub
Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, Spain.
Institute of Biomedical Research of Murcia (IMIB), Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain.
Front Pharmacol. 2020 May 5;11:562. doi: 10.3389/fphar.2020.00562. eCollection 2020.
Verapamil is a phenylalkylamine class calcium channel blocker that for half a century has been used for the treatment of cardiovascular diseases. Nowadays, verapamil is also considered as a drug option for the treatment of several neurological and psychiatric disorders, such as cluster headache, bipolar disorders, epilepsy, and neurodegenerative diseases. Here, we review insights into the potential preventive and therapeutic role of verapamil on Alzheimer's disease (AD) based on limited experimental and clinical data. Pharmacological studies have shown that verapamil has a wide therapeutic spectrum, including antihypertensive, anti-inflammatory, and antioxidative effects, regulation of the blood-brain barrier function, due to its effect on P-glycoprotein, as well as adjustment of cellular calcium homeostasis, which may result in the delay of AD onset or ameliorate the symptoms of patients. However, the majority of the AD individuals are on polypharmacotherapy, and the interactions between verapamil and other drugs need to be considered. Therefore, for an appropriate and successful AD treatment, a personalized approach is more than necessary. A well-known narrow pharmacological window of verapamil efficacy may hinder this approach. It is therefore important to note that the verapamil efficacy may be conditioned by different factors. The onset, grade, and brain distribution of AD pathological hallmarks, the time-sequential appearances of AD-related cognitive and behavioral dysfunction, the chronobiologic and gender impact on calcium homeostasis and AD pathogenesis may somehow be influencing that success. In the future, such insights will be crucial for testing the validity of verapamil treatment on animal models of AD and clinical approaches.
维拉帕米是一种苯烷基胺类钙通道阻滞剂，半个世纪以来一直用于治疗心血管疾病。如今，维拉帕米也被视为治疗多种神经和精神疾病的药物选择，如丛集性头痛、双相情感障碍、癫痫和神经退行性疾病。在此，我们基于有限的实验和临床数据，综述维拉帕米对阿尔茨海默病（AD）潜在预防和治疗作用的相关见解。药理学研究表明，维拉帕米具有广泛的治疗谱，包括降压、抗炎和抗氧化作用，因其对P-糖蛋白的作用而调节血脑屏障功能，以及调节细胞钙稳态，这可能导致AD发病延迟或改善患者症状。然而，大多数AD患者正在接受多种药物治疗，需要考虑维拉帕米与其他药物之间的相互作用。因此，为了进行适当且成功的AD治疗，个性化方法非常必要。维拉帕米疗效的众所周知的狭窄药理学窗口可能会阻碍这种方法。因此，重要的是要注意，维拉帕米的疗效可能受不同因素制约。AD病理特征的发作、程度和脑部分布，AD相关认知和行为功能障碍的时间顺序出现，生物钟和性别对钙稳态及AD发病机制的影响可能在某种程度上影响治疗的成功。未来，这些见解对于在AD动物模型和临床方法中测试维拉帕米治疗的有效性至关重要。
