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氯氮平N-氧化物

氯氮平N-氧化物用途

Clozapine N-oxide (CNO) 是抗精神病药物氯氮平的主要代谢产物。 Clozapine N-oxide是 DREADD 系统的激动剂。

氯氮平N-氧化物名称

[ CAS 号 ]:
34233-69-7

[ 中文名 ]:
MAJORMETABOLITEOFCLOZAPINE.POSSESSESLITTLEORNOACTIVITYAT5-HTRECEPTORS

[ 英文名 ]:
Clozapine N-oxide

[英文别名 ]:

Clozapine N-oxide
Clozapine (N-oxide)

氯氮平N-氧化物生物活性

[ 描述 ]:

Clozapine N-oxide (CNO) 是抗精神病药物氯氮平的主要代谢产物。 Clozapine N-oxide是 DREADD 系统的激动剂。

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 5-HT受体

信号通路 >> 神经信号通路 >> 5-HT受体

研究领域 >> 神经疾病

[ 靶点 ]

DREADD[1]

[体内研究]

在向小鼠单次腹膜内(ip)注射氯氮平N-氧化物(1mg/kg)后,氯氮平N-氧化物(CNO)血浆水平在15分钟达到峰值并且在2小时后非常低。急性给予的CNO可以在其他物种如人和豚鼠中代谢转化为氯氮平。在向表达DREADD的小鼠(或其他物种)长期施用CNO后可能形成的代谢物尚未系统研究。然而,即使在慢性CNO给药后发生向氯氮平的逆转换,应该注意氯氮平是比CNO本身更有效(约10倍)的DREADD激动剂。此外,通过在特定DREADD研究中包括盐水和CNO处理的WT动物,可以容易地鉴定潜在CNO代谢物的混杂生物效应。尽管CNO在小鼠中的血浆半衰期短,但在表达DREADD的实验动物的急性处理后已经描述的生物效应通常更长(6-10小时)。一种可能性是CNO倾向于在组织中累积,尽管其他情况也是可行的[1]。使用一般药代动力学模型进行相互转化过程,氯氮平和氯氮平N-氧化物(CNO)的平均总清除率分别为28.45 L/hr和45.30 L/hr [2]。

[参考文献]

[1]. Wess J, et al. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul;34(7):385-92.

[2]. Chang WH, et al. Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 1998 Jul;22(5):723-39.

[相关活性小分子]

氯氮平N-氧化物物理化学性质

[ 密度 ]:
1.36g/cm3

[ 沸点 ]:
517.4ºC at 760mmHg

[ 熔点 ]:
190-248ºC

[ 分子式 ]:
C₁₈H₁₉ClN₄O

[ 分子量 ]:
342.823

[ 闪点 ]:
266.7ºC

[ 精确质量 ]:
342.124725

[ PSA ]:
57.06000

[ LogP ]:
0.76

[ 折射率 ]:
1.685

[ 储存条件 ]:
2-8℃

氯氮平N-氧化物MSDS

详细MSDS(安全技术说明书)

氯氮平N-氧化物毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: HP1760000

CHEMICAL NAME :: 5H-Dibenzo(b,e)(1,4)diazepine, 8-chloro-11-(4-methyl-1-piperazinyl)-, N-oxide

CAS REGISTRY NUMBER :: 34233-69-7

LAST UPDATED :: 198706

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C18-H19-Cl-N4-O

MOLECULAR WEIGHT :: 342.86

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 245 mg/kg

TOXIC EFFECTS :: Behavioral - ataxia

REFERENCE :: CCCCAK Collection of Czechoslovak Chemical Communications. (Academic Press Inc. Ltd., 24-28 Oval Rd., London NW1 7DX, UK) V.1- 1929- Volume(issue)/page/year: 43,309,1978

氯氮平N-氧化物安全信息

[ 符号 ]:

GHS06

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301-H315-H319-H335

[ 警示性声明 ]:
P261-P301 + P310-P305 + P351 + P338

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

[ 危害码 (欧洲) ]:
Xn: Harmful;

[ 风险声明 (欧洲) ]:
22-36/37/38

[ 安全声明 (欧洲) ]:
26-36

[ 危险品运输编码 ]:
UN 2811 6.1/PG 3

[ RTECS号 ]:
HP1760000

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

氯氮平N-氧化物文献

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Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala...

Side chain flexibilities in the human ether-a-go-go related gene potassium channel (hERG) together with matched-pair binding studies suggest a new binding mode for channel blockers.

J. Med. Chem. 52 , 4266-76, (2009)

The cardiac hERG K(+) channel constitutes a long-standing and expensive antitarget for the drug industry. From a study of the flexibility of hERG around its internal binding cavity, we have developed ...

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