三甲丙咪嗪

三甲丙咪嗪用途

三米帕明是一种5-HT受体拮抗剂,5-HT1C、5-HT2和5-HT1A的pKi结合值分别为6.39、8.10和4.66。三米帕明也是一种有效的选择性抑制剂,靶向人去甲肾上腺素(hNAT)、血清素(hSERT)和有机阳离子转运蛋白(hOCT1、hOCT2),IC50值分别为4.99μM、2.11μM、3.72μM和8.00μM。苯丙胺具有血管活性和抗焦虑功效[1][2][3]。

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三甲丙咪嗪名称

[ CAS 号 ]:
739-71-9

[ 中文名 ]:
曲米帕明

[ 英文名 ]:
trimipramine

[中文别名 ]:

三甲丙咪嗪

[英文别名 ]:

tremin
(+/-)-Trihexyphenidyl hydrochloride
EINECS 212-008-3
Trihexy
triiodothyronine
Trimipramine
paralest
peragit
Sedrina
timipramine

三甲丙咪嗪生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 神经疾病

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

信号通路 >> 抗感染 >> 细菌

[ 靶点 ]

5-HT1C Receptor:6.39 (pKi)

5-HT2 Receptor:8.10 (pKi)

5-HT1A Receptor:4.66 (pKi)

[体外研究]

与5-HT1C受体相比,三米帕明对5-HT2的亲和力要高得多[1]。Trimipramine是人体NAT和SERT的中度抑制剂,IC50值分别为4.99μM和2.11μM[2]。SERT和NAT可代表三米帕明抗抑郁作用的靶点(1mM、0.1mM、1.01 mM、1μM、0 0.1μM；10min；HEK293细胞)[2]。

[体内研究]

三甲基丙胺(5mg/kg/d；14d；慢性给药)在大鼠中起作用：1.增加局部5-HT的浓度。5-HT在额叶皮质和海马中最高,其次是嗅结节和下丘脑。2.减少额叶皮质5-HT2和纹状体DA D2受体的数量。3.脑区域单胺和代谢物水平的增加。因此,表明多巴胺(DA)和5-HT的合成速率更高,与5-HT2和DA D2受体的自适应下调一致[3]。动物模型：雄性Wistar大鼠(220-250g)；在胸背侧肩胛间区皮下植入渗透微型泵[3]剂量：5mg/kg/天给药：通过smotic微型泵给药；14天结果：减少额叶皮质5-HT2和纹状体DA D2受体的数量,从而阻断5-HT和多巴胺(DA)的摄取。

[参考文献]

[1]. Jenck F, et al. Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs. Eur J Pharmacol. 1993 Feb 9. 231(2):223-9.

[2]. Haenisch B, et al. Inhibitory potencies of trimipramine and its main metabolites at human monoamine and organic cation transporters. Psychopharmacology (Berl). 2011 Sep. 217(2):289-95.

[3]. Juorio AV, et al. The effects of chronic trimipramine treatment on biogenic amine metabolism and on dopamine D2, 5-HT2 and tryptamine binding sites in rat brain. Gen Pharmacol. 1990. 21(5):759-62.

三甲丙咪嗪物理化学性质

[ 密度 ]:
0.9912 (rough estimate)

[ 沸点 ]:
426.2°C (rough estimate)

[ 熔点 ]:
45°

[ 分子式 ]:
C₂₀H₂₆N₂

[ 分子量 ]:
294.43400

[ 闪点 ]:
9℃

[ 精确质量 ]:
294.21000

[ PSA ]:
6.48000

[ LogP ]:
4.18600

[ 折射率 ]:
1.6450 (estimate)

[ 储存条件 ]:
2-8°C

三甲丙咪嗪毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: HO1225000

CHEMICAL NAME :: 5H-Dibenz(b,f)azepine, 5-(3-(dimethylamino)-2-methylpropyl)-10,11-dihydro-

CAS REGISTRY NUMBER :: 739-71-9

BEILSTEIN REFERENCE NO. :: 1321466

LAST UPDATED :: 199612

DATA ITEMS CITED :: 6

MOLECULAR FORMULA :: C20-H26-N2

MOLECULAR WEIGHT :: 294.48

WISWESSER LINE NOTATION :: T C676 BN&T&J B1Y1&1N1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 18 mg/kg

TOXIC EFFECTS :: Cardiac - other changes

REFERENCE :: PSDTAP Proceedings of the European Society for the Study of Drug Toxicity. (Princeton, NJ 08540) V.1-15, 1963-74. For publisher information, see PESTD5. Volume(issue)/page/year: 6,171,1965

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 250 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: 102,753,1963

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 145 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :: CRSBAW Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales. (SPPIF, B.P.22, F-41353 Vineuil, France) V.1- 1849- Volume(issue)/page/year: 155,307,1961

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 200 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: 102,753,1963

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 42 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :: CRSBAW Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales. (SPPIF, B.P.22, F-41353 Vineuil, France) V.1- 1849- Volume(issue)/page/year: 155,307,1961

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三甲丙咪嗪安全信息

[ 符号 ]:

GHS02, GHS06, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H225-H301 + H311 + H331-H370

[ 警示性声明 ]:
P210-P260-P280-P301 + P310-P311

[ 危害码 (欧洲) ]:
F,T

[ 风险声明 (欧洲) ]:
11-23/24/25-39/23/24/25

[ 安全声明 (欧洲) ]:
16-36/37-45

[ 危险品运输编码 ]:
UN 3249

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

三甲丙咪嗪合成路线

详细合成路线

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