Background:Scientific evidence to guide clinicians on the use of different antiseizure drugs in combination therapy is either very limited or lacking.In this study,the impact of lacosamide and perampanel alone and in ...Background:Scientific evidence to guide clinicians on the use of different antiseizure drugs in combination therapy is either very limited or lacking.In this study,the impact of lacosamide and perampanel alone and in combination was tested in corneal kindling model in mice,which is a cost-effective mechanism for screening of antiseizure drugs.Methods:The impact of lacosamide(5 mg/kg)and perampanel(0.125 mg/kg)alone and their combination was tested in corneal kindling process(3-mA current for 3 s applied twice daily for consecutive 12 days)in male BALB/c mice.Post-kindling,mice were subjected to a battery of behavioral tests assessing anxiety,memory,and depression-like behaviors.Brain tissues were then harvested for analysis of oxidative stress biomarkers.Results:Our results showed that the combination therapy of lacosamide and perampanel was more effective in reducing seizure progression than monotherapy of these drugs.Animals treated with combination therapy showed significant behavioral improvements,as reduced anxiety and depression were noticed,and their cognitive abilities were notably better compared to animals of all other groups.Moreover,biochemical assays of isolated brains from combination-treated group revealed lesser amount of oxidative stress.In addition,outcomes of dual regime were comparable to the phenytoin in seizure control but showed superior benefits in mitigation of kindling-prompted behavioral dysfunction and oxidative stress.Conclusions:This study suggests that the lacosamide and perampanel combination therapy worked noticeably better in halting the corneal kindling process in mice and improved the epilepsy-associated psychiatric disorders that might be due to antioxidant effects of both drugs.展开更多
Rhenium-188 is prospectively effective for both diagnosis and radiotherapy as it appropriately emits gamma rays and beta particles.Lacosamide(LCM)is a newly approved antiepileptic medication for focal drug-resistant e...Rhenium-188 is prospectively effective for both diagnosis and radiotherapy as it appropriately emits gamma rays and beta particles.Lacosamide(LCM)is a newly approved antiepileptic medication for focal drug-resistant epilepsy.Rhenium-188 was separated with high elution yield and high purity using the new 188W/188Re generator based on the ZrSiW gel matrix.188Re-LCM was prepared with high radiochemical yield and high purity.Biodistribution of 188Re-LCM in normal Swiss albino mice was investigated to determine its utility as a potential brain therapy agent.The 188W/188Re generator was used to obtain 188Re based on the ZrSi188W gel matrix,and the chemical,radiochemical,and radionuclidic purity of the obtained 188Re was determined using inductively coupled plasma optical emission spectrometry(ICP-AES),a paper chromatography technique,and high-purity germanium(HPGe)detection,respectively,to assess its validity for LCM labeling.Various factors,such as the pH,reaction time,and LCM quantity,were therefore studied in order to improve the yield and purity of 188Re-LCM,as determined by various chromatographic techniques such as electrophoresis,thin layer chromatography(TLC),and highpressure liquid chromatography(HPLC).188Re was obtained with a high elution yield(75±3%)and a low 188W breakthrough(0.001±0.0001%).The maximum radiochemical yield of 188Re-LCM(87.5±1.8%)was obtained using 50 ll LCM(4 mM),250 ll stannous chloride(4.4 mM)at pH 4,100 ll 188Re(37 MBq),within 30 min,at room temperature(25±3C),as determined by TLC,electrophoresis,and HPLC techniques.Biodistribution analysis showed that 188Re-LCM was primarily localized in the brain(5.1%)with a long residence time(240 min).展开更多
Lacosamide was prepared by chemical method coupled with enzymatic method. N-Acetyl-D, L-3-methoxy-alanine, derived from D,L-3-methoxy-alanine, was used in the resolution process catalyzed by immobilized Escherichia co...Lacosamide was prepared by chemical method coupled with enzymatic method. N-Acetyl-D, L-3-methoxy-alanine, derived from D,L-3-methoxy-alanine, was used in the resolution process catalyzed by immobilized Escherichia coli cells with aminoacylase（EC3.5.1.14） activity. N-Acetyl-D-3-methoxy-alanine and L-3- methoxy-alanine were obtained from the resolution system. Lacosamide was synthesized by the amidation of N-acetyl-D-3-methoxy-alanine with benzylamine.展开更多
Objective To investigate the effectiveness and safety of lacosamide(LCM)in pregnant women with epilepsy.Methods A retrospective study was conducted involving 6 pregnant women with epilepsy who were treated with LCM at...Objective To investigate the effectiveness and safety of lacosamide(LCM)in pregnant women with epilepsy.Methods A retrospective study was conducted involving 6 pregnant women with epilepsy who were treated with LCM at the Electroencephalogram Monitoring Center of the Department of Neurology,Xijing Hospital of Air Force Military Medical University from January 2022 to June 2023.Their electroclinical characteristics,seizures during pregnancy,breastfeeding,and follow-upwere summarized.Results The 6 patients were aged 22 to 30 years at the time of pregnancy.Three patients were treated with monotherapy,with a daily dose of LCM ranging from 150 mg to 200 mg,while the other 3 patients were treated with combination therapy,with a daily dose of 150 mg.The seizures of 5 patients decreased during pregnancy compared with progestation except for the case 2 without adherence to Medication.No malformations were observed in the newborns,with the Apgar scores of 9-10 at 1 minute and 5 minutes after birth.The infants showed normal growth,development,intelligence,and motor skills in subsequent assessments.Two patients breastfed their infants,1 for 6 months and the other for 14 months by the last follow-up,with a daily LCM dose of 150 mg to 300 mg during the breastfeeding.No adverse reactions were observed in the infants.Conclusion The addition of LCM during pregnancy and lactation shows good effectiveness and safety with no observed birth malformations.展开更多
A catalytic enantioselective three-component Ugi reaction was developed.SPINOL-derived phosphoric acid with bulky 2,4,6-tricyclohexylphenyl groups at the 6,6′positions was found to be the best catalyst to affordα-am...A catalytic enantioselective three-component Ugi reaction was developed.SPINOL-derived phosphoric acid with bulky 2,4,6-tricyclohexylphenyl groups at the 6,6′positions was found to be the best catalyst to affordα-amino amide derivatives in good to excellent yields(62%to 99%)and enantiocontrol(81%to>99%enantiomeric excess).This asymmetric reaction was applicable well to an array of aliphatic aldehydes.The gram-scale synthesis,modification of dapsone,and enantioselective synthesis of(R)-Lacosamide underline the general utility of this methodology.Influence of dihedral angles and substituents of the chiral phosphoric acids on the enantioselectivity was also discussed in this article.展开更多
基金The authors extended their appreciation to Distinguished Scientist Fellowship program at King Saud University,Riyadh,Saudi Arabia,for funding this work through research supporting project number(RSP2024R131).
文摘Background:Scientific evidence to guide clinicians on the use of different antiseizure drugs in combination therapy is either very limited or lacking.In this study,the impact of lacosamide and perampanel alone and in combination was tested in corneal kindling model in mice,which is a cost-effective mechanism for screening of antiseizure drugs.Methods:The impact of lacosamide(5 mg/kg)and perampanel(0.125 mg/kg)alone and their combination was tested in corneal kindling process(3-mA current for 3 s applied twice daily for consecutive 12 days)in male BALB/c mice.Post-kindling,mice were subjected to a battery of behavioral tests assessing anxiety,memory,and depression-like behaviors.Brain tissues were then harvested for analysis of oxidative stress biomarkers.Results:Our results showed that the combination therapy of lacosamide and perampanel was more effective in reducing seizure progression than monotherapy of these drugs.Animals treated with combination therapy showed significant behavioral improvements,as reduced anxiety and depression were noticed,and their cognitive abilities were notably better compared to animals of all other groups.Moreover,biochemical assays of isolated brains from combination-treated group revealed lesser amount of oxidative stress.In addition,outcomes of dual regime were comparable to the phenytoin in seizure control but showed superior benefits in mitigation of kindling-prompted behavioral dysfunction and oxidative stress.Conclusions:This study suggests that the lacosamide and perampanel combination therapy worked noticeably better in halting the corneal kindling process in mice and improved the epilepsy-associated psychiatric disorders that might be due to antioxidant effects of both drugs.
文摘Rhenium-188 is prospectively effective for both diagnosis and radiotherapy as it appropriately emits gamma rays and beta particles.Lacosamide(LCM)is a newly approved antiepileptic medication for focal drug-resistant epilepsy.Rhenium-188 was separated with high elution yield and high purity using the new 188W/188Re generator based on the ZrSiW gel matrix.188Re-LCM was prepared with high radiochemical yield and high purity.Biodistribution of 188Re-LCM in normal Swiss albino mice was investigated to determine its utility as a potential brain therapy agent.The 188W/188Re generator was used to obtain 188Re based on the ZrSi188W gel matrix,and the chemical,radiochemical,and radionuclidic purity of the obtained 188Re was determined using inductively coupled plasma optical emission spectrometry(ICP-AES),a paper chromatography technique,and high-purity germanium(HPGe)detection,respectively,to assess its validity for LCM labeling.Various factors,such as the pH,reaction time,and LCM quantity,were therefore studied in order to improve the yield and purity of 188Re-LCM,as determined by various chromatographic techniques such as electrophoresis,thin layer chromatography(TLC),and highpressure liquid chromatography(HPLC).188Re was obtained with a high elution yield(75±3%)and a low 188W breakthrough(0.001±0.0001%).The maximum radiochemical yield of 188Re-LCM(87.5±1.8%)was obtained using 50 ll LCM(4 mM),250 ll stannous chloride(4.4 mM)at pH 4,100 ll 188Re(37 MBq),within 30 min,at room temperature(25±3C),as determined by TLC,electrophoresis,and HPLC techniques.Biodistribution analysis showed that 188Re-LCM was primarily localized in the brain(5.1%)with a long residence time(240 min).
基金Supported by the National Technology-Innovation Fund(No.02CJ-13-01-16)the Open Fund of State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University, China
文摘Lacosamide was prepared by chemical method coupled with enzymatic method. N-Acetyl-D, L-3-methoxy-alanine, derived from D,L-3-methoxy-alanine, was used in the resolution process catalyzed by immobilized Escherichia coli cells with aminoacylase（EC3.5.1.14） activity. N-Acetyl-D-3-methoxy-alanine and L-3- methoxy-alanine were obtained from the resolution system. Lacosamide was synthesized by the amidation of N-acetyl-D-3-methoxy-alanine with benzylamine.
文摘Objective To investigate the effectiveness and safety of lacosamide(LCM)in pregnant women with epilepsy.Methods A retrospective study was conducted involving 6 pregnant women with epilepsy who were treated with LCM at the Electroencephalogram Monitoring Center of the Department of Neurology,Xijing Hospital of Air Force Military Medical University from January 2022 to June 2023.Their electroclinical characteristics,seizures during pregnancy,breastfeeding,and follow-upwere summarized.Results The 6 patients were aged 22 to 30 years at the time of pregnancy.Three patients were treated with monotherapy,with a daily dose of LCM ranging from 150 mg to 200 mg,while the other 3 patients were treated with combination therapy,with a daily dose of 150 mg.The seizures of 5 patients decreased during pregnancy compared with progestation except for the case 2 without adherence to Medication.No malformations were observed in the newborns,with the Apgar scores of 9-10 at 1 minute and 5 minutes after birth.The infants showed normal growth,development,intelligence,and motor skills in subsequent assessments.Two patients breastfed their infants,1 for 6 months and the other for 14 months by the last follow-up,with a daily LCM dose of 150 mg to 300 mg during the breastfeeding.No adverse reactions were observed in the infants.Conclusion The addition of LCM during pregnancy and lactation shows good effectiveness and safety with no observed birth malformations.
基金supported by the National Natural Science Foundation of China(21825105,21772081)Shenzhen Special Funds for the Development of Biomedicine,Internet,New Energy and New Material Industries(JCYJ20170412151701379,KQJSCX20170328153203)Special Funds for the Cultivation of Guangdong College Students’ Scientific and Technological Innovation(PDJH2019C467)
文摘A catalytic enantioselective three-component Ugi reaction was developed.SPINOL-derived phosphoric acid with bulky 2,4,6-tricyclohexylphenyl groups at the 6,6′positions was found to be the best catalyst to affordα-amino amide derivatives in good to excellent yields(62%to 99%)and enantiocontrol(81%to>99%enantiomeric excess).This asymmetric reaction was applicable well to an array of aliphatic aldehydes.The gram-scale synthesis,modification of dapsone,and enantioselective synthesis of(R)-Lacosamide underline the general utility of this methodology.Influence of dihedral angles and substituents of the chiral phosphoric acids on the enantioselectivity was also discussed in this article.
