吐根碱

吐根碱
臨床資料
AHFS/Drugs.com	国际药品名称
ATC碼	P01AX02 (WHO) QP51AX02;
识别信息
	IUPAC命名法 (2S,3R,11bS)-2[(1R)-6,7-Dimethoxy-1,2,3,4-; tetrahydroisoquinolin-1-yl]methyl3-ethyl-9,10-; dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido; [2,1-a]isoquinoline; ;
CAS号	483-18-1
PubChem CID	10219;
ChemSpider	9802 ;
UNII	X8D5EPO80M;
KEGG	C09421 ;
ChEBI	CHEBI:4781 ;
ChEMBL	ChEMBL50588 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID5022980 ;
ECHA InfoCard	100.006.903
化学信息
化学式	C29H40N2O4
摩尔质量	480.639克/摩尔
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES O(c1cc2c(cc1OC)[C@H](NCC2)C[C@H]5C[C@H]4c3c(cc(OC)c(OC)c3)CCN4C[C@@H]5CC)C;
	InChI InChI=1S/C29H40N2O4/c1-6-18-17-31-10-8-20-14-27(33-3)29(35-5)16-23(20)25(31)12-21(18)11-24-22-15-28(34-4)26(32-2)13-19(22)7-9-30-24/h13-16,18,21,24-25,30H,6-12,17H2,1-5H3/t18-,21-,24+,25-/m0/s1 ; Key:AUVVAXYIELKVAI-CKBKHPSWSA-N ;

吐根碱是一种抗原虫药和呕吐诱导药物，它提取自吐根树，并以其催吐药性而命名。

吐根碱-基于制剂

最早对吐根碱的应用是口服提取自吐根或吐根树根的萃取物，这种萃取物中原本以为只包含了一种生物碱-吐根碱，但后来还发现有吐根酚碱（Cephaeline）、吐根微碱（psychotrine）及其它数种生物碱。虽然这种疗法据说很成功，但萃取物却引起了许多患者的呕吐，从而降低了它的药效。在某些情况下，可通过服用鸦片类药物来减缓恶心症状。其他减轻恶心的建议主要为在吐根碱表面涂覆药物，让它在胃中消化后释放^[1]。

抗阿米巴虫

吐根碱被认为是一种治疗阿米巴病（Amoebiasis）的更有效药物，同时，仍利用它来引起恶心，因为它比吐根树根的粗提取物更有效。此外，吐根碱还可以用于皮下注射来引发恶心，但效果不如口服。

虽然它是一种强效的抗原虫剂，但该药物也会影响肌肉收缩，在某些情况下会导致心脏衰竭。因此，在某些用途中，它需要在医生的监护下使用，以便及时处置不良反应。

去氢土根碱

去氢土根碱又叫去氢依米丁（Dehydroemetine），是一种合成的抗原虫药，其抗阿米巴虫的特性和结构类似于吐根碱（仅乙基旁的双键不同），但是它产生的副作用较少。

吐根酚碱

吐根酚碱又叫头九节因（Cephaeline）也是一种在吐根树根中发现的去甲土根碱。

蛋白质合成阻断应用

在实验室中，通过将吐根碱二氢氯化水合物与40S亚基核糖体的结合，以阻止真核细胞中蛋白质的合成^[2]。因此，可用于对细胞中蛋白质降解的研究。这种化合物能诱发40S亚基核糖体(S14蛋白)耐吐根碱突变体发生改变^[3]^[4]，并显示出具有对小穗苎麻素、异娃儿藤碱和土布洛素的交叉耐药性，而非蛋白质合成的其他抑制体^[5]。化合物所诱发突变体所表现出的交叉耐药性，证明了它们与负责生物活性的吐根碱共享共同的决定性结构^[6]。

生物合成

吐根碱、吐根酚碱的生物合成主要来自两种途径：从酪氨酸合成多巴胺和从牻牛儿焦磷酸（geranyl diphosphate）合成断马钱子苷。生物合成开始于多巴胺与断马钱子苷反应构成Desacetylipecoside（R型）和Deacetylisoipecoside（S型），然后通过皮克特－施彭格勒反应反应和后续一系列的O-甲基化，去除葡萄糖形成中间体。接下来，中间体与另外的多巴胺分子反应形成7'-O-甲基吐根酚碱，最终由7'-O-甲基化吐根酚碱制成吐根酚碱；由6'-O-甲基吐根碱制成吐根碱。^[7]^[8]。

副作用

重度或过度使用吐根碱可能会引发肌病（myopathy）及心肌症（Cardiomyopathy）的风险。

备注

^ Cushny, Arthur Robertson. A Textbook of pharmacology and therapeutics, or the action of drugs in health and disease. Lea and Febiger, New York. 1918: 438–442.
^ (Jimenez et al., Enzymatic and nonenzymatic translocation of yeast polysomes. Site of action of a number of inhibitors. Biochemistry, 1977 16;4727-4730)
^ Gupta, R.S. and Siminovitch. L. (1977). The molecular basis of emetine resistance in Chinese hamster ovary cells: Alteration in the 40S ribosomal subunit. Cell 10: 61-66.
^ Rhoads, D. D. and Roufa, D. J. (1985) Emetine resistance of Chinese hamster cells: structures of wild-type and mutant ribosomal protein S14 mRNAs Mol. Cell. Biol. 5:1655-1659.
^ Gupta, R.S. and Siminovitch, L. (1977). Mutants of CHO cells resistant to the protein synthesis inhibitors, cryptopleurine and tylocrebrine: Genetic and structural evidence for common site of action of emetine, cryptopleurine, tylocrebrine and tubulosine. Biochemistry 16: 3209-3214.
^ Gupta, R.S., Krepinsky, G.H. and Siminovitch, L. (1980). Structural determinants responsible for the biological activity of emetine, cryptopleurine and tylocrebrine: Structure-activity relationship among related compounds. Mol. Pharmacol. 18: 136-143.
^ Cheong, BE; Takemura, T; Yoshimatsu, K; Sato, F. Molecular cloning of an O-methyltransferase from adventitious roots of Carapichea ipecacuanha.. Bioscience, Biotechnology, and Biochemistry. 2011, 75 (1): 107–13. PMID 21228475. doi:10.1271/bbb.100605.
^ Nomura, T; Kutchan, TM. Three New O-Methyltransferases Are Sufficient for All O-Methylation Reactions of Ipecac Alkaloid Biosynthesis in Root Culture of Psychotria ipecacuanha. The Journal of Biological Chemistry. 2010-03-05, 285 (10): 7722–38. PMC 2844217 . PMID 20061395. doi:10.1074/jbc.M109.086157.

[CUSHNY_1918-1] Cushny, Arthur Robertson. A Textbook of pharmacology and therapeutics, or the action of drugs in health and disease. Lea and Febiger, New York. 1918: 438–442.

[2] (Jimenez et al., Enzymatic and nonenzymatic translocation of yeast polysomes. Site of action of a number of inhibitors. Biochemistry, 1977 16;4727-4730)

[3] Gupta, R.S. and Siminovitch. L. (1977). The molecular basis of emetine resistance in Chinese hamster ovary cells: Alteration in the 40S ribosomal subunit. Cell 10: 61-66.

[4] Rhoads, D. D. and Roufa, D. J. (1985) Emetine resistance of Chinese hamster cells: structures of wild-type and mutant ribosomal protein S14 mRNAs Mol. Cell. Biol. 5:1655-1659.

[5] Gupta, R.S. and Siminovitch, L. (1977). Mutants of CHO cells resistant to the protein synthesis inhibitors, cryptopleurine and tylocrebrine: Genetic and structural evidence for common site of action of emetine, cryptopleurine, tylocrebrine and tubulosine. Biochemistry 16: 3209-3214.

[6] Gupta, R.S., Krepinsky, G.H. and Siminovitch, L. (1980). Structural determinants responsible for the biological activity of emetine, cryptopleurine and tylocrebrine: Structure-activity relationship among related compounds. Mol. Pharmacol. 18: 136-143.

[7] Cheong, BE; Takemura, T; Yoshimatsu, K; Sato, F. Molecular cloning of an O-methyltransferase from adventitious roots of Carapichea ipecacuanha.. Bioscience, Biotechnology, and Biochemistry. 2011, 75 (1): 107–13. PMID 21228475. doi:10.1271/bbb.100605.

[8] Nomura, T; Kutchan, TM. Three New O-Methyltransferases Are Sufficient for All O-Methylation Reactions of Ipecac Alkaloid Biosynthesis in Root Culture of Psychotria ipecacuanha. The Journal of Biological Chemistry. 2010-03-05, 285 (10): 7722–38. PMC 2844217 . PMID 20061395. doi:10.1074/jbc.M109.086157.

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