Phosphodiesterase-5 Inhibitors and Dementia Risk: Confounding by Indication in Real-World Studies DOI

Che-Yuan Wu,

Walter Swardfager

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 100(4), P. 1161 - 1163

Published: July 6, 2024

Pharmacoepidemiologic studies using routinely collected data allow researchers to propose drugs for repurposing trials dementia prevention or treatment. A recent cohort study reported a 54% lower risk among users of sildenafil compared certain cardiovascular medications. We caution that "confounding by indication" can arise when outcomes are between drug interest and an inappropriate comparator. Here, we emphasize important considerations in selecting active assess the implications substantial confounding indication pharmacoepidemiologic linking phosphodiesterase-5 inhibitors risk.

Language: Английский

The future of pharmaceuticals: Artificial intelligence in drug discovery and development DOI Creative Commons
Chen Fu, Qi Chen

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101248 - 101248

Published: Feb. 1, 2025

Language: Английский

Citations

1
A new paradigm for drug discovery in the treatment of complex diseases: drug discovery and optimization DOI Creative Commons
Yu Yuan, Lu-Lu Yu, Chenghao Bi

et al.

Chinese Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 24, 2025

Abstract In the past, drug research and development has predominantly followed a "single target, single disease" model. However, clinical data show that single-target drugs are difficult to interfere with complete disease network, prone develop resistance low safety in use. The proposal of multi-target therapy (also known as "cocktail therapy") provides new approach for discovery, which can affect reduce adverse reactions by regulating multiple targets. Natural products an important source innovative development, more than half approved small molecule related natural products. there many challenges process products, such active screening, target identification preclinical dosage optimization. Therefore, how good from always been challenge. This article summarizes applications shortcomings technologies product bioactivity clarify mode action (direct/indirect target), dose Moreover, response faced trend interdisciplinary multi-technology integration, strategy "active substances — optimization" is proposed solve key dimensions levels.

Language: Английский

Citations

0
Phosphodiesterase‑5 inhibitors and Alzheimer’s disease; a meta‑analysis on clinical studies DOI Creative Commons
Saman Behboodi Tanourlouee, Parham Torabinavid,

Ali Vaezi

et al.

Published: April 7, 2025

Abstract To evaluate the potential therapeutic benefits of phosphodiesterase-5 inhibitors (PDE5Is) on Alzheimer’s disease (AD), electronic databases Embase, Scopus, and Medline were systematically searched from inception to March 18th, 2024. Studies assessing association between use PDE5Is AD incidence included. Random-effects model restricted maximum likelihood estimator was used pool data. Seven studies reviewed comprising 4,833,558 individuals, which 348,546 received treatment with one PDE5Is. Pooled hazard ratios (HR) for incidence, comparing no drug (HR = 0.47, 95% CI 0.26–0.82, p -value: 0.01), or drugs not in trial 0.41, 0.33–0.52, <0.01) calculated. Synthesized evidence indicates administration is associated risk reduction, supporting conduct phase 3 clinical trials.

Language: Английский

Citations

0
The Emerging Role of Phosphodiesterase 5 Inhibition in Neurological Disorders: The State of the Art DOI Creative Commons
Clara Crescioli, Maria Paola Paronetto

Cells, Journal Year: 2024, Volume and Issue: 13(20), P. 1720 - 1720

Published: Oct. 17, 2024

Growing evidence suggests that neuroinflammation is not just a consequence of neurodegeneration in pathologies such as Alzheimer’s disease, Parkinson’s Huntington’s disease or Amyotrophic lateral sclerosis, but it rather determinant factor, which plays pivotal role the onset and progression these disorders. Neuroinflammation can affect cells processes central nervous system (CNS) well immune cells, might precede protein aggregation, hallmark neurodegenerative process. Standard treatment methods are far from being able to counteract inflammation delay neurodegeneration. Remarkably, phosphodiesterase 5 inhibitors (PDE5is), represent potent vasoactive drugs used first-line for erectile dysfunction (ED), display important anti-inflammatory effects through cyclic guanosine monophosphate (cGMP) level stabilization. Since PDE5 hydrolyzes cGMP, several studies positioned therapeutic target, more specifically, PDE5is potential alternative strategies variety neurological Indeed, limit enhance synaptic plasticity, with beneficial on cognitive function memory. The aim this review provide an overview some main underlying may be targets PDE5is, focusing sildenafil, most extensively studied. Current using PDEis diseases will summarized.

Language: Английский

Citations

2
Phosphodiesterase-5 Inhibitors and Dementia Risk: A Real-World Study DOI Creative Commons
Naomi Gronich, Nili Stein, Walid I. Saliba

et al.

Neuroepidemiology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 10

Published: June 27, 2024

Biological and scarce epidemiological evidence suggested that phosphodiesterase-5 inhibitors (PDE5i) might reduce dementia risk. We aimed to examine the association between PDE5i using real-world data.

Language: Английский

Citations

1
The Protective Effect of Uridine in a Rotenone-Induced Model of Parkinson’s Disease: The Role of the Mitochondrial ATP-Dependent Potassium Channel DOI Open Access
Galina D. Mironova,

Alexei A. Mosentsov,

Vasyliy V. Mironov

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7441 - 7441

Published: July 6, 2024

The effect of the modulators mitochondrial ATP-dependent potassium channel (mitoKATP) on structural and biochemical alterations in substantia nigra brain tissues was studied a rat model Parkinson’s disease induced by rotenone. It found that, experimental parkinsonism accompanied characteristic motor deficits, both neurons myelin sheath nerve fibers were affected. Changes energy ion exchange mitochondria also revealed. nucleoside uridine, which is source for synthesis mitoKATP opener uridine diphosphate, able to dose-dependently decrease behavioral disorders prevent death animals, occurred about 50% animals model. Uridine prevented disturbances redox, energy, exchanges mitochondria, eliminated their structure nigra. Cytochemical examination showed that restored indicators oxidative phosphorylation glycolysis peripheral blood lymphocytes. specific blocker channel, 5-hydroxydecanoate, positive effects suggesting this involved neuroprotection. Taken together, these findings indicate promise using natural metabolite as new drug and, possibly, stop progression disease.

Language: Английский

Citations

1
Phosphodiesterase-5 Inhibitors and Dementia Risk: Confounding by Indication in Real-World Studies DOI

Che-Yuan Wu,

Walter Swardfager

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 100(4), P. 1161 - 1163

Published: July 6, 2024

Pharmacoepidemiologic studies using routinely collected data allow researchers to propose drugs for repurposing trials dementia prevention or treatment. A recent cohort study reported a 54% lower risk among users of sildenafil compared certain cardiovascular medications. We caution that "confounding by indication" can arise when outcomes are between drug interest and an inappropriate comparator. Here, we emphasize important considerations in selecting active assess the implications substantial confounding indication pharmacoepidemiologic linking phosphodiesterase-5 inhibitors risk.

Language: Английский

Citations

0