ArticleMolecular medicine (Cambridge, Mass.)
Selective antihypertensive dihydropyridines lower Aβ accumulation by targeting both the production and the clearance of Aβ across the blood-brain barrier.
Article in Molecular medicine (Cambridge, Mass.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.
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Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Drug repositioning: Progress and challenges in drug discovery for various diseases.European journal of medicinal chemistry · 2022Pooled it
- Drug repositioning for Alzheimer's disease.Nature reviews. Drug discovery · 2012Pooled it
- Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial.PLoS medicine · 2018Trial
- Trial
- NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease.BMJ open · 2014Trial
- Current updates on latest basic research of scientific relevance in hypertensive dementia.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- Molecular insights into nilvadipine-hemoglobin interactions: conformational dynamics and binding mechanisms.RSC advances · 2025Article
- Transforming Alzheimer's Treatment: Unveiling New Potential with Drug Repurposing Strategies.Current medicinal chemistry · 2025Review
- Transcriptome and Animal Model Integration Reveals Inhibition of Calcium Homeostasis-Associated Gene ITPKB Alleviates Amyloid Plaque Deposition.Journal of molecular neuroscience : MN · 2024Article
- Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.Journal of Alzheimer's disease : JAD · 2024Review
- Therapeutic Potential of Heterocyclic Compounds Targeting Mitochondrial Calcium Homeostasis and Signaling in Alzheimer's Disease and Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2023Review
- L-type calcium channel antagonist isradipine age-dependently decreases plaque associated dystrophic neurites in 5XFAD mouse model.Neuropharmacology · 2023Article
- Role of Oxysterols in the Activation of the NLRP3 Inflammasome as a Potential Pharmacological Approach in Alzheimer's Disease.Current neuropharmacology · 2023Review
- Modulation of L-type calcium channels in Alzheimer's disease: A potential therapeutic target.Computational and structural biotechnology journal · 2023Review
- Effects of Hypertension on Alzheimer's Disease and Related Disorders.Current hypertension reports · 2022Review
- A review of the mechanisms underlying selected comorbidities in Alzheimer's disease.Pharmacological reports : PR · 2021Review
- Influence of traumatic brain injury on extracellular tau elimination at the blood-brain barrier.Fluids and barriers of the CNS · 2021Article
- Article
- Post-Translational Modification of Cav1.2 and its Role in Neurodegenerative Diseases.Frontiers in pharmacology · 2021Review
- Gauging the role and impact of drug interactions and repurposing in neurodegenerative disorders.Current research in pharmacology and drug discovery · 2021Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several large population-based or clinical trial studies have suggested that certain dihydropyridine (DHP) L-type calcium channel blockers (CCBs) used for the treatment of hypertension may confer protection against the development of Alzheimer disease (AD). However, other studies with drugs of the same class have shown no beneficial clinical effects. To determine whether certain DHPs are able to impact underlying disease processes in AD (specifically the accumulation of the Alzheimer Aβ peptide), we investigated the effect of several antihypertensive DHPs and non-DHP CCBs on Aβ production. Among the antihypertensive DHPs tested, a few, including nilvadipine, nitrendipine and amlodipine inhibited Aβ production in vitro, whereas others had no effect or raised Aβ levels. In vivo, nilvadipine and nitrendipine acutely reduced brain Aβ levels in a transgenic mouse model of AD (Tg PS1/APPsw) and improved Aβ clearance across the blood-brain barrier (BBB), whereas amlodipine and nifedipine were ineffective showing that the Aβ-lowering activity of the DHPs is independent of their antihypertensive activity. Chronic oral treatment with nilvadipine decreased Aβ burden in the brains of Tg APPsw (Tg2576) and Tg PS1/APPsw mice, and also improved learning abilities and spatial memory. Our data suggest that the clinical benefit conferred by certain antihypertensive DHPs against AD is unrelated to their antihypertensive activity, but rely on their ability to lower brain Aβ accumulation by affecting both Aβ production and Aβ clearance across the BBB.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.