Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characte...Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses,respec-tively,on corneal kindling-induced generalized seizures and behavioral alterations.Furthermore,observed convulsive frequency and behavioral changes were corre-lated to post-kindling-induced changes in the activity of markers of oxidative stress.Methods:Adult C57BL/6 mice were kindled via twice-daily transcorneal 50-Hz elec-trical stimulations(3 mA)for 3 s for 12 days until animals reached a fully kindled state.After the kindling procedure,animals were tested using a set of behavioral tests,and neurochemical alterations were assessed.Results:Corneal-kindled animals exhibited intense generalized convulsions,altered behavioral phenotypes typified by positive symptoms(hyperlocomotion),negative symptoms(anxiety and anhedonia),and deficits in semantic and working memory.BRV 10+RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4–5 seizures and improved phenotypical deficits,that is,anxiety,depression,and memory impairments.Moreover,this combination therapy mitigated kindling-induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult.Conclusion:Based on our outcomes,this dual therapy provides supporting evidence in alleviating epilepsy-induced neurobehavioral comorbidities and changes in redox homeostasis.展开更多
A stability-indicating RP-HPLC method was developed and validated lbr the determination of Rufinamide in tablet dosage forms using C 18 column （250 mm x 4.6 mm, 5 μm） wilh mobile phase consisting of water acetonitr...A stability-indicating RP-HPLC method was developed and validated lbr the determination of Rufinamide in tablet dosage forms using C 18 column （250 mm x 4.6 mm, 5 μm） wilh mobile phase consisting of water acetonitrile （40：60, v/v） with a [low rate of 0.8 mL/min （UV detection 215 nm）. Linearity was observed over the concentration range 1.0 200 μg/mL （R2=0.9997） with regression equation y-113190 x＋63053. Rufinamide was subjected to stress conditions including acidic, alkaline, oxidation, photolysis and thermal degradation. Rufinaraide is more sensitive towards acidic degradation. The method was validated as per ICH guidelines.展开更多
The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigation...The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigations regarding their pharmacological properties are yet to be performed.Besides,considering their broad anticonvulsant activities,an extension of their therapeutic indications may be worthy of investigation,especially regarding other seizure types as well as other central nervous system disorders.Although different liquid chromatographic(LC)methods coupled with ultraviolet,fluorescence,mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel,retigabine,rufinamide and stiripentol,new and more cost-effective methods are yet required.Therefore,this review summarizes the main analytical aspects regarding the liquid chromatographic methods developed for the analysis of perampanel,retigabine(and its main active metabolite),rufinamide and stiripentol in biological samples and pharmaceutical dosage forms.Furthermore,the physicochemical and stability properties of the target compounds will also be addressed.Thus,this review gathers,for the first time,important background information on LC methods that have been developed and applied for the determination of perampanel,retigabine,rufinamide and stiripentol,which should be considered as a starting point if new(bio)analytical techniques are aimed to be implemented for these drugs.展开更多
Spinal muscular atrophy (SMA) is devastating genetic disease characterized by progressive loss of motor neuron and skeletal muscle weakness. SMA is the most common lethal genetic disease in infancy. SMA is caused by d...Spinal muscular atrophy (SMA) is devastating genetic disease characterized by progressive loss of motor neuron and skeletal muscle weakness. SMA is the most common lethal genetic disease in infancy. SMA is caused by deletion or mutation of SMN1 gene and subsequent lack of SMN protein. Our purpose in this study was to evaluate the therapeutic potential of rufinamide, an antiepileptic drug. In this study, SMA patient-derived fibroblasts and differentiated spinal motor neurons (MNs) using SMA patient-derived iPSCs were used as in vitro SMA model. SMN mRNA was significantly increased by addition of rufinamide in type III SMA patient-derived fibroblasts. Furthermore, rufinamide stimulated neurite elongation in type III SMA patient derived-iPSCs-MNs. In contrast of the result using type III SMA patient-derived fibroblasts, the expression level of SMN mRNA was not changed after rufinamide treatment in type I SMA patient-derived fibroblasts, and rufinamide did not affect neurite outgrowth in type I SMA patients derived-iPSCs-MNs. These findings indicate that rufinamide may be one of the potential candidate drugs for mild type of SMA.展开更多
基金The authors extend their appreciation to the Distinguished Scientist Fellowship program at King Saud University,Riyadh,Saudi Arabia,for funding this work through Research Supporting Project Number RSP2024R131.
文摘Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses,respec-tively,on corneal kindling-induced generalized seizures and behavioral alterations.Furthermore,observed convulsive frequency and behavioral changes were corre-lated to post-kindling-induced changes in the activity of markers of oxidative stress.Methods:Adult C57BL/6 mice were kindled via twice-daily transcorneal 50-Hz elec-trical stimulations(3 mA)for 3 s for 12 days until animals reached a fully kindled state.After the kindling procedure,animals were tested using a set of behavioral tests,and neurochemical alterations were assessed.Results:Corneal-kindled animals exhibited intense generalized convulsions,altered behavioral phenotypes typified by positive symptoms(hyperlocomotion),negative symptoms(anxiety and anhedonia),and deficits in semantic and working memory.BRV 10+RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4–5 seizures and improved phenotypical deficits,that is,anxiety,depression,and memory impairments.Moreover,this combination therapy mitigated kindling-induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult.Conclusion:Based on our outcomes,this dual therapy provides supporting evidence in alleviating epilepsy-induced neurobehavioral comorbidities and changes in redox homeostasis.
文摘A stability-indicating RP-HPLC method was developed and validated lbr the determination of Rufinamide in tablet dosage forms using C 18 column （250 mm x 4.6 mm, 5 μm） wilh mobile phase consisting of water acetonitrile （40：60, v/v） with a [low rate of 0.8 mL/min （UV detection 215 nm）. Linearity was observed over the concentration range 1.0 200 μg/mL （R2=0.9997） with regression equation y-113190 x＋63053. Rufinamide was subjected to stress conditions including acidic, alkaline, oxidation, photolysis and thermal degradation. Rufinaraide is more sensitive towards acidic degradation. The method was validated as per ICH guidelines.
基金supported by Banco Santander/Totta(Portugal)through the fellowship BID/ICI-FCS/CICS/Santander UniversidadesUBI/2017by Foundation for Science and Technology(FCT)through the fellowship SFRH/BD/136028/2018+3 种基金by FEDER funds through the POCI-COMPETE 2020-Operational Program Competitiveness and Internationalization in Axis I(Project No.POCI-01-0145FEDER-007491)National Funds by FCT(Project No.UIDB/00709/2020and Project No.UIDP/00709/2020)the support provided by FEDER funds through the“Programa Operacional do Centro”(Project No.CENTRO-010145-FEDER-000013)。
文摘The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigations regarding their pharmacological properties are yet to be performed.Besides,considering their broad anticonvulsant activities,an extension of their therapeutic indications may be worthy of investigation,especially regarding other seizure types as well as other central nervous system disorders.Although different liquid chromatographic(LC)methods coupled with ultraviolet,fluorescence,mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel,retigabine,rufinamide and stiripentol,new and more cost-effective methods are yet required.Therefore,this review summarizes the main analytical aspects regarding the liquid chromatographic methods developed for the analysis of perampanel,retigabine(and its main active metabolite),rufinamide and stiripentol in biological samples and pharmaceutical dosage forms.Furthermore,the physicochemical and stability properties of the target compounds will also be addressed.Thus,this review gathers,for the first time,important background information on LC methods that have been developed and applied for the determination of perampanel,retigabine,rufinamide and stiripentol,which should be considered as a starting point if new(bio)analytical techniques are aimed to be implemented for these drugs.
文摘Spinal muscular atrophy (SMA) is devastating genetic disease characterized by progressive loss of motor neuron and skeletal muscle weakness. SMA is the most common lethal genetic disease in infancy. SMA is caused by deletion or mutation of SMN1 gene and subsequent lack of SMN protein. Our purpose in this study was to evaluate the therapeutic potential of rufinamide, an antiepileptic drug. In this study, SMA patient-derived fibroblasts and differentiated spinal motor neurons (MNs) using SMA patient-derived iPSCs were used as in vitro SMA model. SMN mRNA was significantly increased by addition of rufinamide in type III SMA patient-derived fibroblasts. Furthermore, rufinamide stimulated neurite elongation in type III SMA patient derived-iPSCs-MNs. In contrast of the result using type III SMA patient-derived fibroblasts, the expression level of SMN mRNA was not changed after rufinamide treatment in type I SMA patient-derived fibroblasts, and rufinamide did not affect neurite outgrowth in type I SMA patients derived-iPSCs-MNs. These findings indicate that rufinamide may be one of the potential candidate drugs for mild type of SMA.
