Late-Stage Dehydroxyazidation of Alcohols Promoted by Trifunctional Hypervalent Azido-Iodine(III) Reagents
Chemistry. 2022 Mar 14. doi: 10.1002/chem.202200272. Online ahead of print.ABSTRACTThe development of convenient new methods for the synthesis of organic azides is highly desirable. Herein, we report a practical method for dehydroxyazidation of alcohols via an S N 2 pathway involving PPh 3 and trifunctional benziodazolone-based hypervalent azido-iodine(III) reagents, which function as an electrophilic center, an azido source, and a base. We successfully used this mild, chemoselective method for late-stage azidation of structurally complex alcohols, as well as for a new synthetic route to the antiepileptic drug rufinamide. ...
Source: Chemistry - March 14, 2022 Category: Chemistry Authors: Xiao-Guang Yang Feng-Huan Du Jun-Jie Li Chi Zhang Source Type: research
Selective stabilization of the intermediate inactivated Na < sup > + < /sup > channel by the new-generation anticonvulsant rufinamide
Biochem Pharmacol. 2022 Jan 19;197:114928. doi: 10.1016/j.bcp.2022.114928. Online ahead of print.ABSTRACTNa+ channels undergo multiple inactivated states with different kinetics, which set the refractory period of neuronal discharges, but isolating the intermediate inactivated state has been challenging. Most classical Na+channel-inhibiting anticonvulsants bind to the fast inactivated state to reduce Na+currents and cellular excitability. These anticonvulsants have the slow binding kinetics and thus necessitate long depolarization for drug action, a "use-dependent" effect sparing most normal activities. Rufinamide is a new...
Source: Biochemical Pharmacology - January 22, 2022 Category: Drugs & Pharmacology Authors: Yun-Chu Lin Yi-Chen Lai Tien-Hung Lin Ya-Chin Yang Chung-Chin Kuo Source Type: research
Selective stabilization of the intermediate inactivated Na < sup > + < /sup > channelby new-generation anticonvulsant rufinamide
Biochem Pharmacol. 2022 Jan 18:114928. doi: 10.1016/j.bcp.2022.114928. Online ahead of print.ABSTRACTNa+ channels undergo multiple inactivated states with different kinetics, which set the refractory period of neuronal discharges, but isolating the intermediate inactivated state has been challenging. Most classical Na+channel-inhibiting anticonvulsants bind to the fast inactivated state to reduce Na+currents and cellular excitability. The slow binding kinetics necessitates long depolarization for drug action, a "use-dependent" effect sparing most normal activities. Rufinamide is a new anticonvulsant targeting Na+channels, ...
Source: Biochemical Pharmacology - January 22, 2022 Category: Drugs & Pharmacology Authors: Yun-Chu Lin Yi-Chen Lai Tien-Hung Lin Ya-Chin Yang Chung-Chin Kuo Source Type: research
HPLC-PDA Identification and Resolution of Rufinamide Forced Degradation Impurities: A Congregated Chemometric Expedite Optimization Coupled with Factorials & amp; Desirability
Biomed Chromatogr. 2022 Jan 21:e5345. doi: 10.1002/bmc.5345. Online ahead of print.ABSTRACTRufinamide (RFN) is used presently to treat Lenaux - Gastaut syndrome. Full factorial design and desirability approach investigated for optimization of hydrolytic stress via response surface curves (RSC's). The degradation impurities were identified and resolved using reversed-phase high-performance liquid-chromatography (RP-HPLC) on the Qualisil® BDS C8 column. Acetonitrile: water (29:71, v/v) was optimized mobile phase used at a flow rate of 1.0 mL/min with detection at a wavelength of 230 nm. RFN depicted appreciable susceptibili...
Source: Biomedical Chromatography : BMC - January 21, 2022 Category: Biomedical Science Authors: Saurabh B Ganorkar Suraj R Chaudhari Preeti S Bobade Sagar M Pawar Atul A Shirkhedkar Source Type: research
Safety and efficacy of rufinamide in children and adults with Lennox-Gastaut syndrome: A post hoc analysis from Study 022
CONCLUSIONS: In this post hoc analysis, adjunctive rufinamide was well tolerated and improved seizure control in patients with LGS, irrespective of age.PMID:34509883 | DOI:10.1016/j.yebeh.2021.108275 (Source: Epilepsy and Behaviour)
Source: Epilepsy and Behaviour - September 12, 2021 Category: Neurology Authors: Alexis Arzimanoglou Milka Pringsheim Gerhard Josef Kluger Pierre Genton Carlos Perdomo Manoj Malhotra Source Type: research
Efficacy and safety of rufinamide as adjunctive therapy in patients with Lennox Gastaut syndrome: A systematic review and Meta-analysis.
Publication date: Available online 9 July 2021Source: SeizureAuthor(s): Indar Kumar Sharawat, Prateek Kumar Panda, Pragnya Panda, Lesa Dawman (Source: Seizure)
Source: Seizure - July 10, 2021 Category: Neurology Source Type: research
Efficacy and safety of rufinamide as adjunctive therapy in patients with Lennox Gastaut syndrome: A systematic review and Meta-analysis.
Lennox –Gastaut syndrome is one of the childhood-onset epilepsy syndromes characterized by a triad of drug-resistant epilepsy with multiple seizure types, with a high seizure burden (predominantly tonic seizure, atonic seizure, atypical absence seizure, and myoclonic seizure), significant psychomotor ret ardation, and slow spike-wave pattern in electroencephalogram (EEG) [1]. Around 20% cases of LGS have a history of epileptic spasms and LGS constitutes 1-4% of all children with epilepsy [2]. No antiseizure medications (ASMs) have been proven to achieve complete seizure freedom uniformly in all case s of LGS. (Source: Se...
Source: Seizure: European Journal of Epilepsy - July 8, 2021 Category: Neurology Authors: Indar Kumar Sharawat, Prateek Kumar Panda, Pragnya Panda, Lesa Dawman Tags: Original article Source Type: research
Rufinamide-Loaded Chitosan Nanoparticles in Xyloglucan-Based Thermoresponsive In Situ Gel for Direct Nose to Brain Delivery
In 2004, the US FDA approved Rufinamide, an anti-epileptic drug under the brand name Banzel®. In 2015, Banzel® received approval for its use in pediatric patients (ages 1–4 years). Rufinamide shows low oral bioavailability due to a low dissolution rate resulting in less of the drug reaching the brain. This has led to the high dose and dosing frequency of Rufinamide. In this work, using the principle of design of experiments (DoE), we have formulated Rufinamide-loaded chitosan nanoparticles and suspended them in a solution of a thermoresponsive polymer–tamarind seed xyloglucan to form a nasal in situ gel for direct n...
Source: Frontiers in Pharmacology - June 21, 2021 Category: Drugs & Pharmacology Source Type: research
Neurocognitive Effects of Antiseizure Medications in Children and Adolescents with Epilepsy
Paediatr Drugs. 2021 May 6. doi: 10.1007/s40272-021-00448-0. Online ahead of print.ABSTRACTImpairments in cognition are common in epilepsy and may be caused or exacerbated by antiseizure medications (ASMs). Positive effects on cognition may also be seen with some ASMs. Cognitive outcomes are of particular concern in children who may be at an increased risk of cognitive adverse effects of treatment. A comprehensive literature search was conducted in PubMed in order to evaluate the evidence for cognitive changes associated with treatment with ASMs in paediatric epilepsy patients. The ASMs considered were those in the current...
Source: Paediatric Drugs - May 6, 2021 Category: Pediatrics Authors: Frank M C Besag Michael J Vasey Source Type: research
Neurocognitive Effects of Antiseizure Medications in Children and Adolescents with Epilepsy
AbstractImpairments in cognition are common in epilepsy and may be caused or exacerbated by antiseizure medications (ASMs). Positive effects on cognition may also be seen with some ASMs. Cognitive outcomes are of particular concern in children who may be at an increased risk of cognitive adverse effects of treatment. A comprehensive literature search was conducted in PubMed in order to evaluate the evidence for cognitive changes associated with treatment with ASMs in paediatric epilepsy patients. The ASMs considered were those in the current edition of the British National Formulary (BNF). For most ASMs, remarkably few stu...
Source: Pediatric Drugs - May 6, 2021 Category: Pediatrics Source Type: research
Anti-seizure medications for Lennox-Gastaut syndrome
CONCLUSIONS: RCTs of monotherapy and head-to-head comparison of add-on ASMs are currently lacking. However, we found high-certainty evidence for overall seizure reduction with add-on lamotrigine and rufinamide, with low-certainty evidence for AE leading to study discontinuation compared with add-on placebo or another add-on ASM. The evidence for other add-on ASMs for overall seizure cessation or reduction was low to very low with high- to low-certainty evidence for AE leading to study discontinuation. Future research should consider outcome reporting of overall seizure reduction (applying automated seizure detection device...
Source: Cochrane Database of Systematic Reviews - April 7, 2021 Category: General Medicine Authors: Francesco Brigo Katherine Jones Christin Eltze Sara Matricardi Source Type: research
Anti-seizure medications for Lennox-Gastaut syndrome
CONCLUSIONS: RCTs of monotherapy and head-to-head comparison of add-on ASMs are currently lacking. However, we found high-certainty evidence for overall seizure reduction with add-on lamotrigine and rufinamide, with low-certainty evidence for AE leading to study discontinuation compared with add-on placebo or another add-on ASM. The evidence for other add-on ASMs for overall seizure cessation or reduction was low to very low with high- to low-certainty evidence for AE leading to study discontinuation. Future research should consider outcome reporting of overall seizure reduction (applying automated seizure detection device...
Source: Cochrane Database of Systematic Reviews - April 7, 2021 Category: General Medicine Authors: Francesco Brigo Katherine Jones Christin Eltze Sara Matricardi Source Type: research
Drug-induced liver injury associated with antiseizure medications from the FDA Adverse Event Reporting System (FAERS)
CONCLUSIONS: The majority of newer generation ASMs were not significantly associated with DILI. Future studies utilizing FAERS in conjunction with other data sources will be critical for the ongoing surveillance of DILI, particularly as newly marketed ASMs continue to enter into widespread clinical use.PMID:33626490 | DOI:10.1016/j.yebeh.2021.107832 (Source: Epilepsy and Behaviour)
Source: Epilepsy and Behaviour - February 24, 2021 Category: Neurology Authors: Brad K Kamitaki Carlos D Minacapelli Pengfei Zhang Christopher Wachuku Kapil Gupta Carolyn Catalano Vinod Rustgi Source Type: research
Drug-induced liver injury associated with antiseizure medications from the FDA Adverse Event Reporting System (FAERS)
CONCLUSIONS: The majority of newer generation ASMs were not significantly associated with DILI. Future studies utilizing FAERS in conjunction with other data sources will be critical for the ongoing surveillance of DILI, particularly as newly marketed ASMs continue to enter into widespread clinical use.PMID:33626490 | DOI:10.1016/j.yebeh.2021.107832 (Source: Epilepsy and Behaviour)
Source: Epilepsy and Behaviour - February 24, 2021 Category: Neurology Authors: Brad K Kamitaki Carlos D Minacapelli Pengfei Zhang Christopher Wachuku Kapil Gupta Carolyn Catalano Vinod Rustgi Source Type: research
Effects of long-term antiepileptic polytherapy on bone biochemical markers in ambulatory children and adolescents and possible benefits of vitamin D supplementation: a prospective interventional study.
CONCLUSIONS: These findings imply a lower bone turnover in the young patients on long-term polytherapy (VPA and add-on-therapy), but after one year's vitamin D intake, bone biochemical markers improved.
PMID: 33472116 [PubMed - as supplied by publisher] (Source: Epilepsy and Behaviour)
Source: Epilepsy and Behaviour - January 17, 2021 Category: Neurology Authors: Papassava M, Siomou E, Nakou I, Cholevas V, Challa A, Tzoufi M Tags: Epilepsy Behav Source Type: research
