10-[2-(1-甲基-2-哌啶基)乙基]-2-(甲基亚磺酰基)-10h-苯并噻嗪

用途

中噻嗪(TPS-23)苯磺酸盐是噻嗪的代谢物(HY-B0965A),用作口服活性吩噻嗪类抗精神病药物。中瑞他嗪苯磺酸盐是人类乙醚-a-go-go相关基因(hERG)通道的有效且快速的开放通道阻断剂,在人类胚胎肾293细胞中以550nM(0 mV)的IC50阻断hERG电流[1]。苯磺酸盐中叠氮嗪可用于研究精神分裂症以及某些其他精神疾病[1][2]。

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名称

[ CAS 号 ]:
32672-69-8

[ 中文名 ]:
10-[2-(1-甲基-2-哌啶基)乙基]-2-(甲基亚磺酰基)-10h-苯并噻嗪

[ 英文名 ]:
Mesoridazine besylate

[英文别名 ]:

Mesoridazine benzenesulfonate

生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 神经疾病

信号通路 >> 跨膜转运 >> 钾通道

[体外研究]

中瑞他嗪以浓度依赖性的方式阻断人乙醚-a-go-go相关基因(HERG)电流(0 mV时IC50=550 nM),在HERG激活和饱和的电压范围内,阻断作用显著增加,导致最大HERG通道激活[1]。中硝嗪(15mM；24h)在裸鼠和猪皮中的总吸收率分别为15.94±4.04%和39.24±5.11%[3]。

[体内研究]

美索里达嗪(15mM；局部给药；一次或每天一次,连续7天)在阻断皮肤疼痛方面显示出有效的活性和长时间的镇痛[3]。在裸鼠背部局部施用6小时后,中硝嗪(15mM)显示皮内浓度为0.34 0.74 nmol/mg[3]。动物模型：8周龄雌性裸鼠[3]剂量：15mM给药：局部给药,一次(镇痛试验)或每天给药,连续7天(刺激试验)。结果：显示镇痛效果。观察到轻微的经表皮水分损失(TEWL)从7.8 g/m2/h增加到9.9 g/m2/h。

[参考文献]

[1]. Zhi Su, et al. Mesoridazine: an open-channel blocker of human ether-a-go-go-related gene K+ channel. J Mol Cell Cardiol. 2004 Jan;36(1):151-60.

[2]. I S M Salih, et al. Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses. Clin Pharmacol Ther. 2007 Nov;82(5):548-54.

[3]. Liu KS, et al. Topically applied mesoridazine exhibits the strongest cutaneous analgesia and minimized skin disruption among tricyclic antidepressants: The skin absorption assessment. Eur J Pharm Biopharm. 2016 Aug;105:59-68.

物理化学性质

[ 沸点 ]:
570.5ºC at 760mmHg

[ 分子式 ]:
C₂₇H₃₂N₂O₄S₃

[ 分子量 ]:
544.74900

[ 闪点 ]:
298.9ºC

[ 精确质量 ]:
544.15200

[ PSA ]:
130.81000

[ LogP ]:
7.78380

MSDS

详细MSDS(安全技术说明书)

毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DB7176700

CAS REGISTRY NUMBER :: 32672-69-8

LAST UPDATED :: 199504

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C21-H26-N2-O-S2.C6-H6-O3-S

MOLECULAR WEIGHT :: 544.79

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 40 mg/kg

TOXIC EFFECTS :: Cardiac - arrhythmias (including changes in conduction) Cardiac - other changes Nutritional and Gross Metabolic - changes in calcium

REFERENCE :: AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038) Volume(issue)/page/year: 17,1074,1988 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6153 No. of Facilities: 92 (estimated) No. of Industries: 2 No. of Occupations: 3 No. of Employees: 4525 (estimated) No. of Female Employees: 4107 (estimated)

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安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302

[ 警示性声明 ]:
P301 + P312 + P330

[ 个人防护装备 ]:
dust mask type N95 (US);Eyeshields;Gloves

[ 危害码 (欧洲) ]:
Xn: Harmful;

[ 风险声明 (欧洲) ]:
22

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

[ RTECS号 ]:
DB7176700

文献

Thioridazine steady-state plasma concentrations are influenced by tobacco smoking and CYP2D6, but not by the CYP2C9 genotype.

Eur. J. Clin. Pharmacol. 59 , 45-50, (2003)

Approximately 7% of Caucasians have genetically impaired activity of the cytochrome P450 enzyme CYP2D6 and are classified as poor metabolizers (PM). The disposition of thioridazine has been related to...

Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.

J. Pharmacol. Exp. Ther. 299 , 83-89, (2001)

Atypical antipsychotic drugs, which are distinguished from typical antipsychotic drugs by a lower incidence of extra-pyramidal side effects and less propensity to elevate serum prolactin levels (e.g.,...

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