拉扎贝胺盐酸盐

拉扎贝胺盐酸盐用途

Lazabemide hydrochloride (Ro 19-6327 hydrochloride) 是单胺氧化酶 B (MAO-B) 的选择性的可逆抑制剂(IC50=0.03 μM),但对 MAO-A (IC50>100 μM) 活性较低。高浓度 Lazabemide 具有抑制单胺摄取的作用,抑制去甲肾上腺素、血清素和多巴胺摄取的 IC50 值分别为 86 μM、123 μM 和 >500 μM。Lazabemide 可用于帕金森和阿尔茨海默病的研究。

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拉扎贝胺盐酸盐名称

[ CAS 号 ]:
103878-83-7

[ 中文名 ]:
拉扎贝胺盐酸盐

[ 英文名 ]:
Lazabemide hydrochloride

[英文别名 ]:

Lazabemide hydrochloride
Ro 19-6327/001
Huwentoxin IV
Tempium
Lazabemide monohydrochloride
Lazabemide HCl
Ro 19-6327

拉扎贝胺盐酸盐生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 神经信号通路 >> 单胺氧化酶

研究领域 >> 神经疾病

[ 靶点 ]

MAO-B:0.4 nM (IC50)

[体外研究]

两种放射性标记抑制剂的体外结合特性表明它们是各自酶的选择性、高亲和力配体。3H-ro19-6327在大鼠大脑皮层的KD和Bmax值分别为18.4nm和3.45pmol/mg蛋白[1]。lazabemide的IC50值分别为：NA摄取86μM；5HT摄取123μM；DA摄取>500μM[1]。Lazabemide(5μM)对人MAO-B和MAO-A的抑制作用分别为6.9nm和>10nm。酶法测定其对大鼠MAO-B和MAO-A的抑制作用分别为37nm和>10μM。拉扎贝胺与L-去甲肾上腺素的不同之处在于它们能够诱导突触体释放内源性单胺类物质。因此,Lazabemide(500μM)诱导的5HT释放量大于L-去甲肾上腺素,但在释放DA方面不如L-去甲肾上腺素有效。相反,lazabemide在5ht和DA释放中几乎完全不活跃[2]。Lazabemide(250nm)对DOPAC的形成有明显的抑制作用,但不能增加50μm L-DOPA的肾小管上皮细胞中新形成DA的积累[3]。

[体内研究]

Lazabemide(3mg/kg)可减轻ichemia再灌注诱导的羟自由基生成,与相应的溶媒治疗对照组相比,Lazabemide预处理显示DOPAC水平降低[4]。

[参考文献]

[1]. Saura J, et al. Quantitative enzyme radioautography with 3H-Ro 41-1049 and 3H-Ro 19-6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain. J Neurosci. 1992 May;12(5):1977-99.

[2]. Bondiolotti GP, et al. In vitro effects on monoamine uptake and release by the reversible monoamine oxidase-B inhibitors lazabemide and N-(2-aminoethyl)-p-chlorobenzamide: a comparison with L-deprenyl. Biochem Pharmacol. 1995 Jun 29;50(1):97-102.

[3]. Guimaraes J, et al. The activity of MAO A and B in rat renal cells and tubules. Life Sci. 1998;62(8):727-37.

[4]. Suzuki T, et al. MAO inhibitors, clorgyline and lazabemide, prevent hydroxyl radical generation caused by brain ischemia/reperfusion in mice. Pharmacology. 1995 Jun;50(6):357-62.

拉扎贝胺盐酸盐物理化学性质

[ 沸点 ]:
397.4ºC at 760mmHg

[ 分子式 ]:
C₈H₁₁Cl₂N₃O

[ 分子量 ]:
236.09800

[ 闪点 ]:
194.2ºC

[ 精确质量 ]:
235.02800

[ PSA ]:
68.01000

[ LogP ]:
2.31670

[ 蒸汽压 ]:
1.59E-06mmHg at 25°C

[ 储存条件 ]:
室温，干燥，密封

拉扎贝胺盐酸盐毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: US4551100

CHEMICAL NAME :: 2-Pyridinecarboxamide, N-(2-aminoethyl)-5-chloro-, hydrochloride

CAS REGISTRY NUMBER :: 103878-83-7

LAST UPDATED :: 199509

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C8-H10-Cl-N3-O.Cl-H

MOLECULAR WEIGHT :: 236.12

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 30 gm/kg

SEX/DURATION :: male 9 week(s) pre-mating female 2 week(s) pre-mating - 3 week(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22(suppl 11),S2785,199