AMPA receptor modulation through sequential treatment with perampanel and aniracetam mitigates post-stroke damage in experimental model of ischemic stroke

Sharma, Hemlata; Reeta, K.H.; Sharma, Uma; Suri, Vaishali; Singh, Sanjay

doi:10.1007/s00210-023-02544-z

Naunyn-Schmiedeberg's Arch Pharmacol

2023

DOI: 10.1007/s00210-023-02544-z

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AMPA receptor modulation through sequential treatment with perampanel and aniracetam mitigates post-stroke damage in experimental model of ischemic stroke

Hemlata Sharma

K.H. Reeta

Uma Sharma

et al.

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Cited by 5 publications

(1 citation statement)

References 63 publications

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“…Aniracetam, in combination with AMPA, increases brain-derived neurotrophic factor (BDNF) [ 4 ], an important trophic factor in the brain that supports healthy memory, neurogenesis, and synaptogenesis [ 5 ]. A recent study from 2023 found that aniracetam, when combined with perampanel, reduces inflammation, and increases BDNF [ 6 ]. Research in humans and animals finds aniracetam has excellent safety, tolerability, and few drug interactions, making it an ideal candidate for the prevention and treatment of Alzheimer’s disease (AD) [ 1, 7 ].…”

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confidence: 99%

Aniracetam: An Evidence-Based Model for Preventing the Accumulation of Amyloid-β Plaques in Alzheimer’s Disease

Love

2024

JAD

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Alzheimer’s disease is the leading cause of dementia in the world. It affects 6 million people in the United States and 50 million people worldwide. Alzheimer’s disease is characterized by the accumulation of amyloid-β plaques (Aβ), an increase in tau protein neurofibrillary tangles, and a loss of synapses. Since the 1990s, removing and reducing Aβ has been the focus of Alzheimer’s treatment and prevention research. The accumulation of Aβ can lead to oxidative stress, inflammation, neurotoxicity, and eventually apoptosis. These insults impair signaling systems in the brain, potentially leading to memory loss and cognitive decline. Aniracetam is a safe, effective, cognitive-enhancing drug that improves memory in both human and animal studies. Aniracetam may prevent the production and accumulation of Aβ by increasing α-secretase activity through two distinct pathways: 1) increasing brain derived neurotrophic factor expression and 2) positively modulating metabotropic glutamate receptors. This is the first paper to propose an evidence-based model for aniracetam reducing the accumulation and production of Aβ.

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Aniracetam: An Evidence-Based Model for Preventing the Accumulation of Amyloid-β Plaques in Alzheimer’s Disease

Love

2024

JAD

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Efficacy of perampanel by etiology in Japanese patients with epilepsy—subpopulation analysis of a prospective post‐marketing observational study

Nakai,

Nishimoto,

Higashibeppu

et al. 2024

Epilepsia Open

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ObjectiveTo examine the efficacy and safety of perampanel (PER) in patients with post‐stroke epilepsy (PSE), brain tumor‐related epilepsy (BTRE), and post‐traumatic epilepsy (PTE) using Japanese real‐world data.MethodsThe prospective post‐marketing observational study included patients with focal seizures with or without focal to bilateral tonic–clonic seizures who received PER combination therapy. The observation period was 24 or 52 weeks after the initial PER administration. The safety and efficacy analysis included 3716 and 3272 patients, respectively. This post hoc analysis examined responder rate (50% reduction in seizure frequency), seizure‐free rate (proportion of patients who achieved seizure‐free), and safety in patients included in the post‐marketing study who had PSE, BTRE, and PTE in the 4 weeks prior to the last observation.ResultsOverall, 402, 272, and 186 patients were included in the PSE, BTRE, and PTE subpopulations, and 2867 controls in the “Other” population (etiologies other than PSE, BTRE, or PTE). Mean modal dose (the most frequently administered dose) values at 52 weeks were 3.38, 3.36, 3.64, and 4.04 mg/day for PSE, BTRE, PTE, and “Other,” respectively; PER retention rates were 56.2%, 54.0%, 52.6%, and 59.7%, respectively. Responder rates (% [95% confidence interval]) were 82% (76.3%–86.5%), 78% (70.8%–83.7%), 67% (56.8%–75.6%), and 50% (47.9%–52.7%) for PSE, BTRE, PTE, and “Other,” respectively, and seizure‐free rates were 71% (64.5%–76.5%), 62% (54.1%–69.0%), 50% (40.6%–60.4%), and 28% (25.8%–30.1%), respectively. Adverse drug reactions tended to occur less frequently in the PSE (14.7%), BTRE (16.5%), and PTE (16.7%) subpopulations than in the “Other” population (26.3%).SignificanceIn real‐world clinical conditions, efficacy and tolerability for PER combination therapy were observed at low PER doses for the PSE, BTRE, and PTE subpopulations.Plain Language SummaryTo find out how well the medication perampanel works and whether it is safe for people who have epilepsy after having had a stroke, brain tumor, or head injury, we used information from real‐life medical situations in Japan. We looked at the data of about 3700 Japanese patients with epilepsy who were treated with perampanel. We found that perampanel was used at lower doses and better at controlling seizures, and had fewer side effects for patients with epilepsy caused by these etiologies than the control group.

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Possible involvement of inflammasomes on the post-stroke cognitive impairment in a mouse model of embolic cerebral infarct

Nomura,

Kurokawa,

Takahashi

et al. 2023

Physiology & Behavior

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AMPA receptor modulation through sequential treatment with perampanel and aniracetam mitigates post-stroke damage in experimental model of ischemic stroke

Cited by 5 publications

References 63 publications

Aniracetam: An Evidence-Based Model for Preventing the Accumulation of Amyloid-β Plaques in Alzheimer’s Disease

Aniracetam: An Evidence-Based Model for Preventing the Accumulation of Amyloid-β Plaques in Alzheimer’s Disease

Efficacy of perampanel by etiology in Japanese patients with epilepsy—subpopulation analysis of a prospective post‐marketing observational study

Possible involvement of inflammasomes on the post-stroke cognitive impairment in a mouse model of embolic cerebral infarct

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