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]。

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

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

三甲丙咪嗪上下游产品

三甲丙咪嗪上游产品

三甲丙咪嗪下游产品

三甲丙咪嗪文献

Evaluation of the matrix effect of different sample matrices for 33 pharmaceuticals by post-column infusion.

J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 1000 , 84-94, (2015)

Matrix effects that occur during quantitative measurement by liquid chromatography mass spectrometry specifically when using electrospray ionization are a widely recognized phenomenon. Sample matrix c...

Antidepressants for patients with tinnitus.

Cochrane Database Syst. Rev. 9 , CD003853, (2012)

This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2006 and previously updated in 2009.Tinnitus is described as the perception of sound or noise in the absence ...

Seizures after single-agent overdose with pharmaceutical drugs: analysis of cases reported to a poison center.

Clin. Toxicol. (Phila.) 52(6) , 629-34, (2014)

Seizures during intoxications with pharmaceuticals are a well-known complication. However, only a few studies report on drugs commonly involved and calculate the seizure potential of these drugs.To id...

更多文献