[논문]Efficacy and pharmacokinetics evaluation of 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as an anti-seizure agent

Hwang, Kyu-Seok; Kan, Hyemin; Kim, Seong Soon; Chae, Jin Sil; Yang, Jung Yoon; Shin, Dae-Seop; Ahn, Se Hwan; Ahn, Jin Hee; Cho, Jin-Hwa; Jang, Il-Sung; Shin, Junnyeong; Joo, Jaeyoung; Kim, Cheol-Hee; Bae, Myung Ae

doi:10.1016/j.neuint.2020.104870

[해외논문] Efficacy and pharmacokinetics evaluation of 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as an anti-seizure agent

Neurochemistry international, v.141, 2020년, pp.104870 -

Hwang, Kyu-Seok (Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology) , Kan, Hyemin (Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology) , Kim, Seong Soon (Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology) , Chae, Jin Sil (Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology) , Yang, Jung Yoon (Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology) , Shin, Dae-Seop (Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology) , Ahn, Se Hwan (Department of Chemistry, Gwangju Institute of Science and Technology) , Ahn, Jin Hee (Department of Chemistry, Gwangju Institute of Science and Technology) , Cho, Jin-Hwa (Department of Ph) , Jang, Il-Sung , Shin, Junnyeong , Joo, Jaeyoung , Kim, Cheol-Hee , Bae, Myung Ae

Abstract ▼ AI-Helper

Abstract Epilepsy is a common chronic neurological disease characterized by recurrent epileptic seizures. A seizure is an uncontrolled electrical activity in the brain that can cause different levels of behavior, emotion, and consciousness. One-third of patients fail to receive sufficient seizure control, even though more than fifty FDA-approved anti-seizure drugs (ASDs) are available. In this study, we attempted small molecule screening to identify potential therapeutic agents for the treatment of seizures using seizure-induced animal models. Through behavioral phenotype-based screening, 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) was identified as a prototype. GM-90432 treatment effectively decreased seizure-like behaviors in zebrafish and mice with chemically induced seizures. These results were consistent with decreased neuronal activity through immunohistochemistry for pERK in zebrafish larvae. Additionally, electroencephalogram (EEG) analysis revealed that GM-90432 decreases seizure-specific EEG events in adult zebrafish. Moreover, we revealed the preferential binding of GM-90432 to voltage-gated Na+ channels using a whole-cell patch clamp technique. Through pharmacokinetic analysis, GM-90432 effectively penetrated the blood-brain barrier and was distributed into the brain. Taken together, we suggest that GM-90432 has the potential to be developed into a new ASD candidate. Highlights 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) was identified as an anti-seizure agent. GM-90432 effectively decreased seizure-like behaviors in zebrafish and mouse. Electroencephalogram analysis revealed that GM-90432 mitigate seizure-specific events in adult zebrafish. Electrophysiology analysis implied preferential binding of GM-90432 to voltage-gated Na+ channel. Pharmacokinetic analysis suggested that GM-90432 has the potential to be developed into a new ASD candidate.

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참고문헌 (42)

PloS One Afrikanova 8 2013 10.1371/journal.pone.0054166 Validation of the zebrafish pentylenetetrazol seizure model: locomotor versus electrographic responses to antiepileptic drugs

상세보기
Trends Pharmacol. Sci. Akaike 24 44 2003 10.1016/S0165-6147(02)00010-X Techniques: applications of the nerve-bouton preparation in neuropharmacology

상세보기
Curr. Pharmaceut. Des. Armijo 11 1975 2005 10.2174/1381612054021006 Ion channels and epilepsy

상세보기
Brain Res. Backus 548 41 1991 10.1016/0006-8993(91)91104-9 Action of diazepam on the voltage-dependent Na+ current. Comparison with the effects of phenytoin, carbamazepine, lidocaine and flumazenil

상세보기
Epilepsy Behav. Banote 27 212 2013 10.1016/j.yebeh.2013.01.018 Oral gabapentin suppresses pentylenetetrazole-induced seizure-like behavior and cephalic field potential in adult zebrafish

상세보기
Nat. Commun. Baraban 4 2410 2013 10.1038/ncomms3410 Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment

상세보기
Neurosci Baraban 131 759 2005 10.1016/j.neuroscience.2004.11.031 Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression

상세보기
J. Pharm. Pharmacol. Begley 48 136 1996 10.1111/j.2042-7158.1996.tb07112.x The blood-brain barrier: principles for targeting peptides and drugs to the central nervous system

상세보기
CNS Drugs Brodie 31 527 2017 10.1007/s40263-017-0441-0 Sodium channel blockers in the treatment of epilepsy

상세보기
Annu. Rev. Pharmacol. Toxicol. Catterall 54 317 2014 10.1146/annurev-pharmtox-011112-140232 Sodium channels, inherited epilepsy, and antiepileptic drugs

상세보기
Sci. Rep. Cho 7 18112 2017 10.1038/s41598-017-16993-z Zebrafish as an animal model in epilepsy studies with multichannel EEG recordings

상세보기
J. Neurosci. Methods Cunliffe 260 91 2016 10.1016/j.jneumeth.2015.07.015 Building a zebrafish toolkit for investigating the pathobiology of epilepsy and identifying new treatments for epileptic seizures

상세보기
CNS Drugs Curia 23 555 2009 10.2165/00023210-200923070-00002 Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders

상세보기
Curr. Protoc. Neurosci. Dhir 58 9 2012 10.1002/0471142301.ns0937s58 Pentylenetetrazol (PTZ) kindling model of epilepsy

상세보기
J. Pharmacol. Exp. Therapeut. Everett 81 402 1944 Comparative anticonvulsive action of 3,5,5-trimethyloxazolidine-2,4-dione (Tridione), Dilantin and phenobarbital
Hum. Mutat. Frints 40 2270 2019 10.1002/humu.23841 Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenital

상세보기
Expert Syst. Appl. Gandhi 37 3513 2010 10.1016/j.eswa.2009.10.036 Expert model for detection of epileptic activity in EEG signature

상세보기
P T Goldenberg 35 392 2010 Overview of drugs used for epilepsy and seizures
Zebrafish Grush 1 46 2004 10.1089/154585404774101671 The efficacy of clove oil as an anesthetic for the zebrafish, Danio rerio (Hamilton)

상세보기
Neuroscience Jang 138 25 2006 10.1016/j.neuroscience.2005.11.001 Presynaptic GABAA receptors facilitate spontaneous glutamate release from presynaptic terminals on mechanically dissociated rat CA3 pyramidal neurons

상세보기
Zebrafish Kim 14 322 2017 10.1089/zeb.2016.1392 Zebrafish as a screening model for testing the permeability of blood-brain barrier to small molecules

상세보기
J. Pharmacol. Exp. Therapeut. Lang 266 829 1993 Lamotrigine, phenytoin and carbamazepine interactions on the sodium current present in N4TG1 mouse neuroblastoma cells
Neurochem. Res. Löscher 42 1873 2017 10.1007/s11064-017-2222-z Animal models of seizures and epilepsy: past, present and future role for the discovery of antiseizure drugs

상세보기
Epilepsia Macdonald 36 Suppl. 2 S2 1995 10.1111/j.1528-1157.1995.tb05996.x Antiepileptic drug mechanisms of action

상세보기
Hum. Mol. Genet. May 24 4848 2015 10.1093/hmg/ddv208 ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons

상세보기
Neurosci. Lett. Murase 103 56 1989 10.1016/0304-3940(89)90485-0 Excitatory and inhibitory amino acids and peptide-induced responses in acutely isolated rat spinal dorsal horn neurons

상세보기
Eur. J. Pharmacol. Nakamura 855 175 2019 10.1016/j.ejphar.2019.05.007 Effects of cenobamate (YKP3089), a newly developed anti-epileptic drug, on voltage-gated sodium channels in rat hippocampal CA3 neurons

상세보기
Expet Opin. Pharmacother. Patsalos 13 699 2012 10.1517/14656566.2012.667803 Pharmacotherapy of the third-generation AEDs: lacosamide, retigabine and eslicarbazepine acetate

상세보기
Dis. Model. Mech. Phillips 7 739 2014 10.1242/dmm.015545 Zebrafish models in translational research: tipping the scales toward advancements in human health

상세보기
Electroencephalogr. Clin. Neurophysiol. Racine 32 281 1972 10.1016/0013-4694(72)90177-0 Modification of seizure activity by electrical stimulation. II: motor seizure

상세보기
Nat. Methods Randlett 12 1039 2015 10.1038/nmeth.3581 Whole-brain activity mapping onto a zebrafish brain atlas

상세보기
Curr. Drug Metabol. Reichel 7 183 2006 10.2174/138920006775541525 The role of blood-brain barrier studies in the pharmaceutical industry

상세보기
J. Neurosci. Roy 12 2104 1992 10.1523/JNEUROSCI.12-06-02104.1992 Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons

상세보기
Epilepsia Scheffer 58 512 2017 10.1111/epi.13709 ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology

상세보기
Curr. Med. Chem. Schlossauer 2 175 2002 Comparative anatomy, physiology and in vitro models of the blood-brain and blood-retina barrier
Curr. Opin. Neurol. Schmidt 25 159 2012 10.1097/WCO.0b013e3283507e73 Evidence-based review on the natural history of the epilepsies

상세보기
Epileptic Disord. Sills 3 165 2001 10.1684/j.1950-6945.2001.tb00392.x Update on the mechanisms of action of antiepileptic drugs

상세보기
IEEE Trans. Inf. Technol. Biomed. Tzallas 13 703 2009 10.1109/TITB.2009.2017939 Epileptic seizure detection in EEGs using time-frequency analysis

상세보기
Seizure Veauthier 18 392 2009 10.1016/j.seizure.2009.02.001 Impact of levetiracetam add-on therapy on different EEG occipital frequencies in epileptic patients

상세보기
Westerfield 2000 The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Danio Rerio)
Epilepsia Wilcox 54 Suppl. 4 23 2013 Issues related to development of new antiseizure treatments
World Health Organization

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[해외논문] Efficacy and pharmacokinetics evaluation of 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as an anti-seizure agent

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[해외논문] Efficacy and pharmacokinetics evaluation of 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as an anti-seizure agent

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