司替戊醇

司替戊醇用途

Stiripentol (STP)是一种抗惊厥剂,其可以抑制由 CYP3A4(非竞争性)和 CYP2C19(竞争性地)介导的 CLB 向 N-desmethylclobazam(NCLB)的 N-去甲基化,其 Ki 值分别为 1.59±0.07 和 0.516±0.065 μM,IC50 值分别为 1.58 和 3.29 μM。

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司替戊醇名称

[ CAS 号 ]:
49763-96-4

[ 中文名 ]:
斯利潘托

[ 英文名 ]:
Stiripentol

[中文别名 ]:

司替戊醇

[英文别名 ]:

Stiripentol
Stiripentol [USAN:INN]
UNII:R02XOT8V8I

司替戊醇生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 代谢酶/蛋白酶 >> 细胞色素P450

研究领域 >> 神经疾病

[ 靶点 ]

IC50: 1.58 μM (CYP3A4), 3.29 μM (CYP2C19)[1] Ki: 1.59±0.07μM (CYP3A4), 0.516±0.065 μM (CYP2C19)[1]

[体外研究]

Stiripentol(STP)是一种抗惊厥药,可以抑制CLB对由CYP3A4(非竞争性)和CYP2C19(竞争性)介导的N-去甲基clobazam(NCLB)的N-去甲基化。 Stiripentol(STP)对CLB去甲基化的抑制最好通过表达CYP3A4的表达Ki =1.6μM的非竞争性抑制模型和表达cDNA的CYP2C19的Ki =0.52μM的竞争性抑制模型来描述。通过表达cDNA的CYP2C19从NCLB形成OH-NCLB被Stiripentol(STP)竞争性抑制,Ki =0.14μM[1]。

[体内研究]

在用Stiripentol(STP)单一疗法治疗的小鼠中,BT1(39.67±1.09℃)和BT2(41.32±1.05℃)之间的差异达到统计学显着性(t = 3.097,p <0.05)。 Stiripentol(STP)单药治疗与CLB单药治疗之间BT2的差异具有统计学意义(t = 2.615,p <0.05)。在用Stiripentol(STP)+ CLB联合治疗的小鼠中,BT1(40.18±0.58℃)和BT2(43.03±0.49℃)之间的差异达到统计学显着性(t = 10.44,p <0.01)[2]。

[细胞实验]

使用各种浓度的CLB（2,10,20,40,60和100μM）和增加浓度的Stiripentol（STP）测定了Stiripentol（STP）对CYP3A4和CYP2C19进行CLB去甲基化的抑制常数（表观Ki）（ 0,0.5,1,2和5μM）。关于CYP2C19的NCLB羟基化，用不同浓度的NCLB（1.5,4,6,8,12和14μM）和STP（0,0.1,0.5,1和2μM）类似地测定表观Ki。 IC50值通过在治疗血浆浓度范围内浓度（2μMCLB或14μMNCLB）与浓度增加的Stiripentol（STP）（0.001,0.002,0.005,0.01,0.05,0.1,0.25）的浓度来确定，2,5和10μM）[1]。

[动物实验]

在该实验中指定了Scn1aRX / +小鼠的两个年龄组，p1M（n = 18，年龄4周）和p5M（n = 18，年龄5-10个月）。两组均随机分为3个亚组（n = 6），每个亚组仅给予Stiripentol（STP）（300 mg / kg），单用CLB（6.62 mg / kg）或Stiripentol（STP）组合（p1M） ; 150mg / kg，p5M; 300mg / kg）和CLB（6.62mg / kg）。在从基线癫痫发作研究中恢复48小时后，通过腹膜内注射（ip）施用所有药物。在给予CLB或STP + CLB后1小时和20分钟收集血液样品，分别测量CLB和N-去甲基clobazam的血浆浓度[2]。

[参考文献]

[1]. Giraud C, et al. In vitro and in vivo inhibitory effect of stiripentol on clobazam metabolism.Drug Metab Dispos. 2006 Apr;34(4):608-11. Epub 2006 Jan 13.

[2]. Cao D, et al. Efficacy of stiripentol in hyperthermia-induced seizures in a mouse model of Dravet syndrome. Epilepsia. 2012 Jul;53(7):1140-5.

[相关活性小分子]

司替戊醇物理化学性质

[ 密度 ]:
1.1±0.1 g/cm3

[ 沸点 ]:
365.4±11.0 °C at 760 mmHg

[ 熔点 ]:
73-74ºC

[ 分子式 ]:
C₁₄H₁₈O₃

[ 分子量 ]:
234.291

[ 闪点 ]:
174.8±19.3 °C

[ 精确质量 ]:
234.125595

[ PSA ]:
38.69000

[ LogP ]:
3.39

[ 外观性状 ]:
白色固体

[ 蒸汽压 ]:
0.0±0.9 mmHg at 25°C

[ 折射率 ]:
1.579

[ 储存条件 ]:
<0°C;避免加热

司替戊醇MSDS

详细MSDS(安全技术说明书)

司替戊醇毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: SB3393000

CHEMICAL NAME :: 1-Penten-3-ol, 4,4-dimethyl-1-(3,4-methylenedioxyphenyl)-

CAS REGISTRY NUMBER :: 49763-96-4

BEILSTEIN REFERENCE NO. :: 1313047

LAST UPDATED :: 199612

DATA ITEMS CITED :: 6

MOLECULAR FORMULA :: C14-H18-O3

MOLECULAR WEIGHT :: 234.32

WISWESSER LINE NOTATION :: T56 BO DO CHJ G1U1YQX1&1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >3 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 34,199,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1471 mg/kg

TOXIC EFFECTS :: Behavioral - anticonvulsant

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 34,199,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 34,199,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1250 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: EJMCA5 European Journal of Medicinal Chemistry--Chimie Therapeutique. (Editions Scientifiques Elsevier, 29 rue Buffon, F-75005, Paris, France) V.9- 1974- Volume(issue)/page/year: 13,41,1978

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 72 mg/kg

TOXIC EFFECTS :: Behavioral - anticonvulsant

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 34,199,1984 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6400 mg/kg

SEX/DURATION :: female 2 week(s) pre-mating - 18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: REPTED Reproductive Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1987- Volume(issue)/page/year: 7,439,1993

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司替戊醇安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302

[ 危险品运输编码 ]:
NONH for all modes of transport

司替戊醇文献

The efficacy of bromides, stiripentol and levetiracetam in two patients with malignant migrating partial seizures in infancy.

Epileptic Disord. 13(1) , 22-6, (2011)

The syndrome of malignant migrating partial seizures in infancy is a devastating, age-specific, epileptic encephalopathy, which still presents an aetiological, pathophysiological and therapeutic probl...

Stiripentol in refractory status epilepticus.

Epilepsia 54 Suppl 6 , 103-5, (2013)

Benzodiazepines (BZDs), which enhance γ-aminobutyric acid (GABAA ) receptor-mediated inhibition, are the first-line therapy for treatment of status epilepticus (SE). However, pharmacoresistance to BZD...

[Clinical and genetic diagnosis of Dravet syndrome: report of 20 cases].

Ideggyogy. Sz. 61(11-12) , 402-8, (2008)

Severe myoclonic epilepsy in infancy (SMEI; Dravet's syndrome) is a malignant epilepsy syndrome characterized by prolonged febrile hemiconvulsions or generalized seizures starting in the first year of...

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