Evaluating bexicaserin for the treatment of developmental epileptic encephalopathies

被引:0
作者
Dell'isola, Giovanni Battista [1 ]
Verrotti, Alberto [1 ]
Sciaccaluga, Miriam [2 ,3 ]
Roberti, Roberta [4 ]
Parnetti, Lucilla [2 ]
Russo, Emilio [4 ]
Costa, Cinzia [2 ]
机构
[1] Univ Perugia, Dept Pediat, Menghini Sq 1, I-06129 Perugia, Italy
[2] Univ Perugia, Dept Med & Surg, Sect Neurol, Lab Expt Neurol, Perugia, Italy
[3] Mauro Baschirotto Rare Dis Fdn BIRD Onlus, Longare, VI, Italy
[4] Univ Magna Grecia Catanzaro, Sci Hlth Dept, Catanzaro, Italy
关键词
Bexicaserin (LP352); developmental and epileptic encephalopathies (DEE); drug-resistant epilepsy (DRE); antiseizure medication (ASM); serotonin; 5-HT2C; 5-HT2C RECEPTOR LIGANDS; FEEDING-BEHAVIOR; SEROTONIN; 5-HT; RAT MODEL; IN-VITRO; ANTICONVULSANT; FLUOXETINE; 5-HYDROXYTRYPTAMINE; AGONIST; LORCASERIN;
D O I
10.1080/14656566.2024.2373350
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
IntroductionDevelopmental epileptic encephalopathies (DEEs) pose significant challenges due to their refractory nature and limited treatment options. Despite advancements in genetic understanding, effective therapies targeting underlying pathophysiology are lacking. Serotoninergic dysfunction has been implicated in epilepsy, sparking interest in serotonin as a therapeutic target.Area coveredThis article explores the potential of bexicaserin, a selective 5-HT2C receptor agonist, as an adjunctive antiseizure medication in DEEs. Bexicaserin is thought to modulate GABAergic neurotransmission, suppressing central hyperexcitability. Preclinical studies demonstrate its efficacy across various seizure models. Clinical trials, including the Pacific Study, reveal promising results in reducing motor seizures. However, challenges such as adverse effects and treatment discontinuation underscore the need for further investigation.Expert opinionThe efficacy of 5-HT2C serotoninergic agonists, validated in preclinical and clinical studies, highlights serotonin's role in DEEs. Bexicaserin offers new therapeutic possibilities, potentially synergizing with existing antiseizure medications. Polypharmacotherapy, targeting distinct pathways, may enhance therapeutic outcomes. Monitoring pharmacological interactions and addressing central nervous system comorbidities are crucial for optimizing treatment strategies. Further research is needed to elucidate bexicaserin's mechanisms and potential antiepileptogenic effects.
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收藏
页码:1121 / 1130
页数:10
相关论文
共 95 条
[1]   Global increases in seizure susceptibility in mice lacking 5-HT2C receptors:: A behavioral analysis [J].
Applegate, CD ;
Tecott, LH .
EXPERIMENTAL NEUROLOGY, 1998, 154 (02) :522-530
[2]   Enhanced propagation of epileptiform activity through the kindled dentate gyrus [J].
Behr, J ;
Lyson, KJ ;
Mody, I .
JOURNAL OF NEUROPHYSIOLOGY, 1998, 79 (04) :1726-1732
[3]  
BERG KA, 1994, MOL PHARMACOL, V46, P477
[4]   A conservative, single-amino acid substitution in the second cytoplasmic domain of the human serotonin2C receptor alters both ligand-dependent and -independent receptor signaling [J].
Berg, Kelly A. ;
Dunlop, John ;
Sanchez, Teresa ;
Silva, Michelle ;
Clarke, William P. .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2008, 324 (03) :1084-1092
[5]   Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): II. Drugs in more advanced clinical development [J].
Bialer, Meir ;
Johannessen, Svein, I ;
Koepp, Matthias J. ;
Levy, Rene H. ;
Perucca, Emilio ;
Perucca, Piero ;
Tomson, Torbjorn ;
White, H. Steve .
EPILEPSIA, 2022, 63 (11) :2883-2910
[6]   Lorcaserin for Dravet Syndrome: A Potential Advance Over Fenfluramine? [J].
Bialer, Meir ;
Perucca, Emilio .
CNS DRUGS, 2022, 36 (02) :113-122
[7]   Improved everyday executive functioning following profound reduction in seizure frequency with fenfluramine: Analysis from a phase 3 long-term extension study in children/young adults with Dravet syndrome [J].
Bishop, Kim I. ;
Isquith, Peter K. ;
Gioia, Gerard A. ;
Gammaitoni, Arnold R. ;
Farfel, Gail ;
Galer, Bradley S. ;
Nabbout, Rima ;
Wirrell, Elaine C. ;
Polster, Tilman ;
Sullivan, Joseph .
EPILEPSY & BEHAVIOR, 2021, 121
[8]   ANTICONVULSANT COMPOUNDS AND 5-HYDROXYTRYPTAMINE IN RAT BRAIN [J].
BONNYCASTLE, DD ;
GIARMAN, NJ ;
PAASONEN, MK .
BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY, 1957, 12 (02) :228-231
[9]  
Borowicz KK, 2006, PHARMACOL REP, V58, P83
[10]   Theta oscillations in the hippocampus [J].
Buzsáki, G .
NEURON, 2002, 33 (03) :325-340