异莰胺

异莰胺用途

美加明是一种口服活性、非选择性、非竞争性nAChR拮抗剂。甲淀粉酶也是一种神经节阻断剂。甲淀粉酶可以穿过血脑屏障。甲淀粉酶可用于神经精神障碍、高血压、抗抑郁药领域的研究[1][2][5]。

异莰胺名称

[ CAS 号 ]:
60-40-2

[ 中文名 ]:
美卡拉明

[ 英文名 ]:
methyl(2,3,3-trimethyltrinorbornan-2-yl)amine

[中文别名 ]:

[英文别名 ]:

EINECS 200-476-1

异莰胺生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 心血管疾病

信号通路 >> 免疫及炎症 >> 组胺受体

信号通路 >> 跨膜转运 >> 胆碱受体

信号通路 >> 神经信号通路 >> 胆碱受体

研究领域 >> 神经疾病

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 组胺受体

[ 靶点 ]

nAChR[1], histamine receptor[2]

[体外研究]

美加明(0.5-9μM,巴斯给药)增加了已识别的5-HT DRN神经元的放电频率[1]。甲淀粉酶(0.5-9μM,巴斯给药)增加5-HT DRN神经元的谷氨酸能并减少GABA能输入[1]。甲淀粉酶(1mM,5min)阻断组胺受体和组胺诱导的兔主动脉螺旋切割条的收缩[2]。甲淀粉酶胺(10μM,48小时)减弱尼古丁的神经保护作用[3]。甲淀粉酶(1-100nM,30min)剂量依赖性地减弱HDMVEC中内皮管的形成[4]。Western印迹分析[3]细胞系：[3]浓度：10μM孵育时间：48小时结果：减少尼古丁促进的ERK1/2的增加。

[体内研究]

甲淀粉酶(皮下泵,50 mg/kg/天,2天)抑制CNV小鼠模型中的脉络膜新生血管(CNV)[4]。美卡明(腹腔注射,0.5-1 mg/kg)在C57BL/6J小鼠的TST(尾部悬吊试验)和FST(强迫游泳试验)中均具有抗抑郁作用,其依赖于β2和α7亚基[5]。动物模型：脉络膜新生血管(CNV)小鼠模型[1]剂量：50 mg/kg/天,2天给药：皮下泵植入背部皮肤下方),200μL,平均泵送速率为0.5μL/h。结果：在不存在尼古丁的情况下,抑制了Bruch膜破裂处CNV的发展。动物模型：C57BL/6J小鼠[5]剂量：0.5-1mg/kg给药：腹腔注射结果：对β2敲除小鼠和α7敲除小鼠没有影响,但减少了FST中野生型同窝小鼠的不动时间。

[参考文献]

[1]. Omar Hernández-González, et al. Mechanisms of stimulatory effects of mecamylamine on the dorsal raphe neurons. Brain Res Bull. 2020 Nov;164:289-298.

[2]. C P Robinson, et al. The influence of mecamylamine on contractions induced by different agonists and on the role of calcium ions in the isolated rabbit aorta. J Pharmacol Exp Ther. 1976 Apr;197(1):57-65.

[3]. Mahadevappa P Badanavalu, et al. Nicotine is neuroprotective to neonatal neurons of sympathetic ganglion in rat. Auton Neurosci. 2019 Jan;216:25-32.

[4]. Katsuji Kiuchi, et al. Mecamylamine suppresses Basal and nicotine-stimulated choroidal neovascularization. Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1705-11.

[5]. Rabenstein RL, et al. The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not beta2- or alpha7-nicotinic acetylcholine receptor subunit knockout mice. Psychopharmacology (Berl). 2006 Dec;189(3):395-401.

异莰胺物理化学性质

[ 密度 ]:
0.91

[ 沸点 ]:
189.3ºC at 760 mmHg

[ 熔点 ]:
245-256ºC

[ 分子式 ]:
C₁₁H₂₁N

[ 分子量 ]:
167.29100

[ 闪点 ]:
58.1ºC

[ 精确质量 ]:
167.16700

[ PSA ]:
12.03000

[ LogP ]:
2.81150

[ 折射率 ]:
1.4875

异莰胺毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: RB6880000

CHEMICAL NAME :: 2-Norbornanamine, N,2,3,3-tetramethyl-

CAS REGISTRY NUMBER :: 60-40-2

LAST UPDATED :: 199703

DATA ITEMS CITED :: 4

MOLECULAR FORMULA :: C11-H21-N

MOLECULAR WEIGHT :: 167.33

WISWESSER LINE NOTATION :: L55 ATJ CM1 C1 D1 D1

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 :: 90 mg/kg

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

REFERENCE :: BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 103,490,1964

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 40 mg/kg

TOXIC EFFECTS :: Behavioral - sleep

REFERENCE :: AITEAT Archivum Immunologiae et Therapiae Experimentalis. (Ars Polona, POB 1001, 00-068 Warsaw 1, Poland) V.10- 1962- Volume(issue)/page/year: 10,905,1962

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 37500 ug/kg

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

REFERENCE :: FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939- Volume(issue)/page/year: 25,163,1962

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 11900 ug/kg

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

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4168308

异莰胺制备

由莰烯与硫氰酸钠作用后经还原而制得。

异莰胺