卡立氨酯(Carisbamate) - 药物靶点：Neurotransmitter receptor_在研适应症：Langer-Giedion综合征，Lennox-Gastaut综合征，癫痫发作_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Carisbamate (USAN)、Comfyde

+ [3]

靶点

Neurotransmitter receptor

作用机制

神经递质受体调节剂

治疗领域

神经系统疾病遗传病与畸形皮肤和肌肉骨骼疾病+ [1]

在研适应症

Langer-Giedion综合征Lennox-Gastaut综合征癫痫发作

非在研适应症

糖尿病性神经病变糖尿病周围神经病变耐药性癫痫+ [7]

原研机构

SK Biopharmaceuticals Co., Ltd.

在研机构

SK Life Science, Inc.

SK Biopharmaceuticals Co., Ltd.

Johnson & Johnson

非在研机构

Janssen Research & Development LLCJohnson & Johnson Pharmaceutical Research & Development LLC

ALZA Corp.

+ [1]

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)无进展

特殊审评孤儿药 (美国)

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结构/序列

分子式C9H10ClNO3

InChIKeyOLBWFRRUHYQABZ-MRVPVSSYSA-N

CAS号194085-75-1

关联

29

项与卡立氨酯相关的临床试验

NCT05219617

/ Recruiting临床3期

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Carisbamate (YKP509) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults, With Optional Open-Label Extension

The primary objective is to evaluate the efficacy of carisbamate (YKP509) as adjunctive treatment in reducing the number of drop seizures (tonic, atonic, and tonic-clonic) compared with placebo in pediatric and adult subjects (age 4-55 years) diagnosed with Lennox Gastaut Syndrome (LGS).

开始日期2022-04-28

申办/合作机构

SK Life Science, Inc.

NCT04520360

/ Completed临床1期

A Single-Center, Open-Label,Randomized, Crossover Study to Evaluate the Relative Bioavailability and Food Effect of a New Oral Suspension and Tablet Formulation of Carisbamate (YKP509) in Healthy Adult Subjects

This study is designed to examine the relative bioavailability of three carisbamate formulations (Oral Suspension Type 1, Oral Suspension Type 2, and a 300 mg Oral Tablet) and to assess the effect of food on the oral bioavailability of the Oral Suspension Type 2 and the 300 mg Oral Tablet.

开始日期2020-08-27

申办/合作机构

SK Life Science, Inc.

[+1]

NCT04062981

/ Completed临床1期

Phase 1, Open-Label Study of Carisbamate in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome

Open-label extension study from YKP509C001 to evaluate the safety and tolerability of carisbamate in subjects with Lennox-Gastaut Syndrome (LGS).

开始日期2019-05-03

申办/合作机构

SK Life Science, Inc.

100 项与卡立氨酯相关的临床结果

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100 项与卡立氨酯相关的转化医学

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100 项与卡立氨酯相关的专利（医药）

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74

项与卡立氨酯相关的文献（医药）

2023-08-02·Biomedicines

Modulating Hyperpolarization-Activated Cation Currents through Small Molecule Perturbations: Magnitude and Gating Control.

Review

作者: Chen, Cheng-Shih ; Wu, Sheng-Nan ; So, Edmund Cheung

The hyperpolarization-activated cation current (I_h) exhibits a slowly activating time course of the current (I_h) when the cell membrane is hyperpolarized for an extended duration. It is involved in generating electrical activity in various excitable cells. Numerous structurally distinct compounds or herbal drugs have the potential to impact both the magnitude and gating kinetics of this current. Brivaracetam, a chemical analog of levetiracetam known to be a ligand for synaptic vesicle protein 2A, could directly suppress the I_h magnitude. Carisbamate, an anticonvulsant agent, not only inhibited the I_h amplitude but also reduced the strength of voltage-dependent hysteresis (Hys_(V)) associated with I_h. Cilobradine, similar to ivabradine, inhibited the amplitude of I_h; however, it also suppressed the amplitude of delayed-rectifier K⁺ currents. Dexmedetomidine, an agonist of α2-adrenergic receptor, exerted a depressant action on I_h in a concentration-dependent fashion. Suppression of I_h amplitude was observed when GAL-021, a breathing control modulator, was present at a concentration exceeding 30 μM. Lutein, one of the few xanthophyll carotenoids, was able to suppress the I_h amplitude as well as to depress Hys_(V)'s strength of I_h. Pirfenidone, a pyridine derivative known to be an anti-fibrotic agent, depressed the I_h magnitude in a concentration- and voltage-dependent fashion. Tramadol, a synthetic centrally active analgesic, was shown to reduce the I_h magnitude, independent of its interaction with opioid receptors. Various herbal drugs, including ent-kaurane-type diterpenoids from Croton tonkinensis, Ganoderma triterpenoids, honokiol, and pterostilbene, demonstrated efficacy in reducing the magnitude of I_h. Conversely, oxaliplatin, a platinum-based chemotherapeutic compound, was observed to effectively increase the I_h amplitude. Collectively, the regulatory effects of these compounds or herbal drugs on cellular function can be partly attributed to their perturbations on I_h.

2023-01-01·Frontiers in cellular neuroscience

Concerted suppressive effects of carisbamate, an anti-epileptic alkyl-carbamate drug, on voltage-gated Na⁺ and hyperpolarization-activated cation currents.

Article

作者: Hung, Te-Yu ; Wu, Sheng-Nan ; Huang, Chin-Wei

Carisbamate (CRS, RWJ-333369) is a new anti-seizure medication. It remains unclear whether and how CRS can perturb the magnitude and/or gating kinetics of membrane ionic currents, despite a few reports demonstrating its ability to suppress voltage-gated Na⁺ currents. In this study, we observed a set of whole-cell current recordings and found that CRS effectively suppressed the voltage-gated Na⁺ (I_Na) and hyperpolarization-activated cation currents (I_h) intrinsically in electrically excitable cells (GH₃ cells). The effective IC₅₀ values of CRS for the differential suppression of transient (I_Na(T)) and late I_Na (I_Na(L)) were 56.4 and 11.4 μM, respectively. However, CRS strongly decreased the strength (i.e., Δarea) of the nonlinear window component of I_Na (I_Na(W)), which was activated by a short ascending ramp voltage (V_ramp); the subsequent addition of deltamethrin (DLT, 10 μM) counteracted the ability of CRS (100 μM, continuous exposure) to suppress I_Na(W). CRS strikingly decreased the decay time constant of I_Na(T) evoked during pulse train stimulation; however, the addition of telmisartan (10 μM) effectively attenuated the CRS (30 μM, continuous exposure)-mediated decrease in the decay time constant of the current. During continued exposure to deltamethrin (10 μM), known to be a pyrethroid insecticide, the addition of CRS resulted in differential suppression of the amplitudes of I_Na(T) and I_Na(L). The amplitude of I_h activated by a 2-s membrane hyperpolarization was diminished by CRS in a concentration-dependent manner, with an IC₅₀ value of 38 μM. For I_h, CRS altered the steady-state I-V relationship and attenuated the strength of voltage-dependent hysteresis (Hys_(V)) activated by an inverted isosceles-triangular V_ramp. Moreover, the addition of oxaliplatin effectively reversed the CRS-mediated suppression of Hys_(V). The predicted docking interaction between CRS and with a model of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel or between CRS and the hNa_V1.7 channel reflects the ability of CRS to bind to amino acid residues in HCN or hNa_V1.7 channel via hydrogen bonds and hydrophobic interactions. These findings reveal the propensity of CRS to modify I_Na(T) and I_Na(L) differentially and to effectively suppress the magnitude of I_h. I_Na and I_h are thus potential targets of the actions of CRS in terms of modulating cellular excitability.

2023-01-01·Therapeutic Advances in Neurological Disorders

Pharmacological diversity amongst approved and emerging antiseizure medications for the treatment of developmental and epileptic encephalopathies

Review

作者: Sills, Graeme J.

Developmental and epileptic encephalopathies (DEEs) are rare neurodevelopmental disorders characterised by early-onset and often intractable seizures and developmental delay/regression, and include Dravet syndrome and Lennox–Gastaut syndrome (LGS). Rufinamide, fenfluramine, stiripentol, cannabidiol and ganaxolone are antiseizure medications (ASMs) with diverse mechanisms of action that have been approved for treating specific DEEs. Rufinamide is thought to suppress neuronal hyperexcitability by preventing the functional recycling of voltage-gated sodium channels from the inactivated to resting state. It is licensed for adjunctive treatment of seizures associated with LGS. Fenfluramine increases extracellular serotonin levels and may reduce seizures via activation of specific serotonin receptors and positive modulation of the sigma-1 receptor. Fenfluramine is licensed for adjunctive treatment of seizures associated with Dravet syndrome and LGS. Stiripentol is a positive allosteric modulator of type-A gamma-aminobutyric acid (GABAA) receptors. As a broad-spectrum inhibitor of cytochrome P450 enzymes, its antiseizure effects may additionally arise through pharmacokinetic interactions with co-administered ASMs. Stiripentol is licensed for treating seizures associated with Dravet syndrome in patients taking clobazam and/or valproate. The mechanism(s) of action of cannabidiol remains largely unclear although multiple targets have been proposed, including transient receptor potential vanilloid 1, G protein-coupled receptor 55 and equilibrative nucleoside transporter 1. Cannabidiol is licensed as adjunctive treatment in conjunction with clobazam for seizures associated with Dravet syndrome and LGS, and as adjunctive treatment of seizures associated with tuberous sclerosis complex. Like stiripentol, ganaxolone is a positive allosteric modulator at GABAA receptors. It has recently been licensed in the USA for the treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder. Greater understanding of the causes of DEEs has driven research into the potential use of other novel and repurposed agents. Putative ASMs currently in clinical development for use in DEEs include soticlestat, carisbamate, verapamil, radiprodil, clemizole and lorcaserin.

100 项与卡立氨酯相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06573	卡立氨酯	N03AX19	DB12338

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
癫痫发作	临床3期	西班牙	SK Life Science, Inc.	2022-04-28
癫痫发作	临床3期	葡萄牙	SK Life Science, Inc.	2022-04-28
癫痫发作	临床3期	波兰	SK Life Science, Inc.	2022-04-28
癫痫发作	临床3期	阿根廷	SK Life Science, Inc.	2022-04-28
癫痫	临床3期	欧盟	Johnson & Johnson Pharmaceutical Research & Development LLC	-
癫痫	临床3期	美国	Johnson & Johnson Pharmaceutical Research & Development LLC	-
Lennox-Gastaut综合征	临床3期	-	SK Biopharmaceuticals Co., Ltd.	-
癫痫部分性运动性发作	临床1期	-	SK Life Science, Inc.	2009-01-01
癫痫持续状态	临床1期	-	SK Life Science, Inc.	2009-01-01
癫痫的复杂部分性发作	临床1期	-	SK Life Science, Inc.	2006-11-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02435381 (CTgov)	临床1/2期	酗酒	11	Placebo (Placebo)	選齋築積齋獵襯遞選鬱(糧鑰廠淵遞鏇鑰蓋鏇鏇) = 願餘簾製顧鏇遞壓壓壓製獵築廠觸襯艱鹹淵繭 (襯窪築廠鏇鬱鹹鹽鑰簾, 觸衊遞遞鹽構構廠鏇襯 ~ 鏇夢窪鑰淵夢範範齋顧) 更多	-	2021-03-02
				Carisbamate (Carisbamate)	選齋築積齋獵襯遞選鬱(糧鑰廠淵遞鏇鑰蓋鏇鏇) = 廠餘壓壓鑰廠蓋鹽廠衊製獵築廠觸襯艱鹹淵繭 (襯窪築廠鏇鬱鹹鹽鑰簾, 遞廠齋襯壓醖窪餘鏇醖 ~ 鏇簾鏇遞糧遞蓋鑰蓋構) 更多
NCT00740623 (Pubmed \| Epilepsia)	临床3期	癫痫部分性发作	547	Carisbamate 800 mg/day	願顧夢鑰觸膚窪繭遞餘(觸遞範餘製鏇製憲廠壓) = Dizziness was the most common treatment-emergent adverse event, with a higher incidence (≥ 5% difference) in the combined carisbamate group (31%) than placebo (9%); the incidence was higher with carisbamate 1,200 mg (32%, n = 58) than with carisbamate 800 mg (30%, n = 53) 鑰顧簾艱糧網遞築醖醖 (積觸鑰積鑰獵廠壓獵簾 )	不佳	2011-04-01
				Carisbamate 1,200 mg/day
IEC2009	N/A	癫痫部分性发作	-	Carisbamate 400mg/day	鬱醖製鏇範製艱選夢鹹(齋壓鹹醖鹽簾鑰衊夢鑰) = low behavioral/psychiatric adverse event rates 簾獵遞蓋壓獵製醖遞廠 (築醖艱鏇遞夢獵鑰衊範 ) 更多	积极	2009-07-02
IEC2009	N/A	癫痫部分性发作	419	Carisbamate 400-800 mg/day	獵餘鹹獵選淵觸齋艱簾(遞艱選範廠願憲廠襯鏇) = low behavioral/psychiatric adverse event rates 遞艱鑰鬱餘簾範繭繭糧 (築襯鹹憲鑰廠齋繭衊齋 ) 更多	积极	2009-07-02