The challenges of treating epilepsy with 25 antiepileptic drugs

Santulli, Lia; Coppola, Antonietta; Balestrini, Simona; Striano, Salvatore

doi:10.1016/j.phrs.2016.03.016

Cited by 77 publications

(58 citation statements)

References 88 publications

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“…Standard solutions (1 mg mL À1 )o fe ach compound were prepared in analyticalgrade acetonitrile and were analyzed at l = 214 and 254 nm. 1 HNMR, 13 CNMR, and 19 FNMR spectra were obtained with aV arian Mercury spectrometer (Varian Inc.,P alo Alto, CA, USA) in CDCl 3 or DMSO operating at 300,75, and 282 MHz, respectively.C hemical shifts are reported in d (ppm) relative to tetramethylsilane (d H = 0ppm) as an internal standard. The J values are expressed in hertz (Hz).…”

Section: Methodsmentioning

confidence: 99%

“…An ACQUITY UPLC BEH C18, 1.7 mm, 2.1 100 mm column was used (Waters, Milford, USA). 1 HNMR, 13 CNMR, 19 FNMR, and LC-MS spectra for selected final compounds are shown in the Supporting Information. Preparative column chromatography was performed by using silica gel 60 (particle size 0.063-0.200;7 0-230 mesh ATM) purchased from Merck (Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…Approximately 50 millionp eople worldwide suffer from epilepsy,a nd this makes it one of the most common neurological diseases globally.E pilepsy is defined as ac hronic disordero f the brain involving recurrents eizures, which are brief episodes of involuntaryt remors. [1] Despite the fact that throughout the recent decades an ew generation of antiepilepticd rugs (AEDs) has been introduced to clinicalu se, seizures are controlled inadequately in up to 30 %o fp atients with epilepsy.M oreover, currentlya vailable medicaments can trigger an umber of serious adverse effects such as diminished attention span and impaired memory function, intelligence,a nd language skills, all of which significantly decrease the quality of life of the patient. [2] Consequently,t he need to identify more effective and less toxic antiepileptic drugs stillexists.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Determination of Lipophilicity, Anticonvulsant Activity, and Preliminary Safety of 3‐Substituted and 3‐Unsubstituted N‐[(4‐Arylpiperazin‐1‐yl)alkyl]pyrrolidine‐2,5‐dione Derivatives

et al. 2017

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A new series of 1,3-substituted pyrrolidine-2,5-dione derivatives as potential anticonvulsant agents are described. Initial pharmacological screening of these compounds was performed by using acute models of seizures (MES and scPTZ tests) in mice after intraperitoneal administration. Quantitative pharmacological research revealed that the most promising compounds were N-[{4-(3-trifluoromethylphenyl)piperazin-1-yl}propyl]-3-benzhydrylpyrrolidine-2,5-dione monohydrochloride (11) with a ED value of 75.9 mg kg (MES test) and N-[{4-(3,4-dichlorophenyl)piperazin-1-yl}ethyl]-3-methylpyrrolidine-2,5-dione monohydrochloride (18) with ED =88.2 mg kg (MES test) and ED =65.7 kg mg (scPTZ test). These compounds displayed a more beneficial protective index than well-known antiepileptic drugs. A plausible mechanism of action of compounds 11 and 18 [molecule 11 blocked the sodium channel (site 2) and 18 blocked both the sodium (site 2) and L-type calcium channels] and their preliminary safety in vitro were evaluated. Besides, the lipophilicity of all synthesized compounds was determined by using UPLC-MS.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis and Determination of Lipophilicity, Anticonvulsant Activity, and Preliminary Safety of 3‐Substituted and 3‐Unsubstituted N‐[(4‐Arylpiperazin‐1‐yl)alkyl]pyrrolidine‐2,5‐dione Derivatives

et al. 2017

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“…[3][4][5][6][7] In the laboratory, the combination of zonisamide, which modulates voltage-sensitive sodium channels and T-type calcium currents, and perampanel, a non-competitive α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid (AMPA) receptor antagonist, has resulted in a marked synergistic anticonvulsant effect in a rat amygdala kindling model of chronic epilepsy, suggesting the potential for increased efficacy. [3][4][5][6][7] In the laboratory, the combination of zonisamide, which modulates voltage-sensitive sodium channels and T-type calcium currents, and perampanel, a non-competitive α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid (AMPA) receptor antagonist, has resulted in a marked synergistic anticonvulsant effect in a rat amygdala kindling model of chronic epilepsy, suggesting the potential for increased efficacy.…”

mentioning

confidence: 99%

“…act on multiple drug targets, and reduce AEs by avoiding AED combinations with similar MoAs that can induce or exacerbate AEs, particularly older drugs with less favorable pharmacokinetic profiles. [3][4][5][6][7] In the laboratory, the combination of zonisamide, which modulates voltage-sensitive sodium channels and T-type calcium currents, and perampanel, a non-competitive α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid (AMPA) receptor antagonist, has resulted in a marked synergistic anticonvulsant effect in a rat amygdala kindling model of chronic epilepsy, suggesting the potential for increased efficacy. 8 Exploration of the interactions between perampanel and other commonly administered AEDs was done in a drug-resistant amygdala kindling model.…”

mentioning

confidence: 99%

Perampanel, an AMPA receptor antagonist: From clinical research to practice in clinical settings

Tsai¹,

Leung

et al. 2017

Acta Neurol Scand

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Epileptic seizures are refractory to treatment in approximately one-third of patients despite the recent introduction of many newer antiepileptic drugs (AEDs). Development of novel AEDs therefore remains a high priority. Perampanel is a first-in-class non-competitive selective AMPA receptor antagonist with a unique mechanism of action. Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with/without secondary generalization (±SG) and primary generalized tonic-clonic (PGTC) seizures have been established in five phase 3 randomized controlled trials (RCTs), and a long-term extension study, and perampanel is approved as monotherapy for focal seizures ±SG in the USA. In patients with focal seizures ±SG, add-on perampanel resulted in median percent reduction in seizure frequency 23.3%-34.5% and ≥50% responder rate 28.5%-37.6%; in PGTC seizures, these results were 76.5% and 64.2%, respectively. Efficacy among adolescents (reduction in seizure frequency 34.8%-35.6%; ≥50% responder rate 40.9%-45.0%) and elderly people (reduction in seizure frequency 12.5%-16.9%; ≥50% responder rate 22.2%-42.9%) is similar to those in adults, and results remain comparable between Asian (reduction in seizure frequency 17.3%-38.0%) and global populations. Perampanel has been extensively studied in real-world clinical practice, with similar efficacy and safety results to the RCTs (≥50% responder rate 12.8%-75.0%; adverse events of somnolence/sedation, dizziness, ataxia, and behavioral changes). Real-world observational studies suggest that perampanel tolerability can be improved by slow titration (2 mg every 2-4 weeks), and bedtime administration can mitigate somnolence and dizziness. Counseling about the potential for behavioral changes and close monitoring are recommended.

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Genetically Engineered Viral Vectors and Organic‐Based Non‐Viral Nanocarriers for Drug Delivery Applications

Hajebi

Yousefiasl

Rahimmanesh

et al. 2022

Adv Healthcare Materials

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Conventional drug delivery systems are challenged by concerns related to systemic toxicity, repetitive doses, drug concentrations fluctuation, and adverse effects. Various drug delivery systems are developed to overcome these limitations. Nanomaterials are employed in a variety of biomedical applications such as therapeutics delivery, cancer therapy, and tissue engineering. Physiochemical nanoparticle assembly techniques involve the application of solvents and potentially harmful chemicals, commonly at high temperatures. Genetically engineered organisms have the potential to be used as promising candidates for greener, efficient, and more adaptable platforms for the synthesis and assembly of nanomaterials. Genetically engineered carriers are precisely designed and constructed in shape and size, enabling precise control over drug attachment sites. The high accuracy of these novel advanced materials, biocompatibility, and stimuli‐responsiveness, elucidate their emerging application in controlled drug delivery. The current article represents the research progress in developing various genetically engineered carriers. Organic‐based nanoparticles including cellulose, collagen, silk‐like polymers, elastin‐like protein, silk‐elastin‐like protein, and inorganic‐based nanoparticles are discussed in detail. Afterward, viral‐based carriers are classified, and their potential for targeted therapeutics delivery is highlighted. Finally, the challenges and prospects of these delivery systems are concluded.

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The challenges of treating epilepsy with 25 antiepileptic drugs

Cited by 77 publications

References 88 publications

Synthesis and Determination of Lipophilicity, Anticonvulsant Activity, and Preliminary Safety of 3‐Substituted and 3‐Unsubstituted N‐[(4‐Arylpiperazin‐1‐yl)alkyl]pyrrolidine‐2,5‐dione Derivatives

Synthesis and Determination of Lipophilicity, Anticonvulsant Activity, and Preliminary Safety of 3‐Substituted and 3‐Unsubstituted N‐[(4‐Arylpiperazin‐1‐yl)alkyl]pyrrolidine‐2,5‐dione Derivatives

Perampanel, an AMPA receptor antagonist: From clinical research to practice in clinical settings

Genetically Engineered Viral Vectors and Organic‐Based Non‐Viral Nanocarriers for Drug Delivery Applications

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