Abstract
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.
Highlights
Alzheimer’s disease (AD) is one of the most widespread types of irreversible dementia among the older population
Ex Vivo Studies It has been demonstrated that verapamil ameliorated the neurotoxicity caused by Ab and reduces the Ab1–40 oligomer levels by improving their efflux from the LS-180 cells, via Pglycoprotein up-regulation (Abuznait et al, 2011)
Physiological studies indicated that the Ab25–35-induced depression of long-term potentiation (LTP) in a hippocampal slice preparation may be attenuated by verapamil (Freir et al, 2003)
Summary
Alzheimer’s disease (AD) is one of the most widespread types of irreversible dementia among the older population. Mutation in the apolipoprotein E (ApoE) gen, is related to the sporadic late-onset variation of AD (age > 65 years) This form, present in the majority of AD population, is considered multifactorial, since both genetic predisposition and several other factors contribute to the progression of the disease. The neuropathological hallmarks are accompanied by extensive microglia cells and astrocyte activation, the key event in neuroinflammation (McGeer et al, 1989; Eikelenboom et al, 1994; Popović et al, 1998a; Henaka et al, 2015; Kim et al, 2019) These cells produce cytokines (interleukins (ILs), tumor necrosis factors (TNFs), transforming growth factors (TGFs), and interferons (IFN). The aim of this mini review is to bring together data about the potential effects of verapamil on the prevention and therapy of AD, and highlights some concerns for future research
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