吐根鹼

吐根鹼
臨床資料
AHFS/Drugs.com	國際藥品名稱
ATC碼	P01AX02 (WHO) QP51AX02;
識別資訊
	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號	483-18-1
PubChem CID	10219;
ChemSpider	9802 ;
UNII	X8D5EPO80M;
KEGG	C09421 ;
ChEBI	CHEBI:4781 ;
ChEMBL	ChEMBL50588 ;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID5022980 ;
ECHA InfoCard	100.006.903
化學資訊
化學式	C29H40N2O4
摩爾質量	480.639克/摩爾
3D模型（JSmol（英語：JSmol））	交互式圖像;
	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 ;

吐根鹼是一種抗原蟲藥和嘔吐誘導藥物，它提取自吐根樹，並以其催吐藥性而命名。

吐根鹼-基於製劑

最早對吐根鹼的應用是口服提取自吐根或吐根樹根的萃取物，這種萃取物中原本以為只包含了一種生物鹼-吐根鹼，但後來還發現有吐根酚鹼（Cephaeline）、吐根微鹼（psychotrine）及其它數種生物鹼。雖然這種療法據說很成功，但萃取物卻引起了許多患者的嘔吐，從而降低了它的藥效。在某些情況下，可通過服用鴉片類藥物來減緩噁心症狀。其他減輕噁心的建議主要為在吐根鹼表面塗覆藥物，讓它在胃中消化後釋放^[1]。

抗阿米巴蟲

吐根鹼被認為是一種治療阿米巴病（Amoebiasis）的更有效藥物，同時，仍利用它來引起噁心，因為它比吐根樹根的粗提取物更有效。此外，吐根鹼還可以用於皮下注射來引發噁心，但效果不如口服。

雖然它是一種強效的抗原蟲劑，但該藥物也會影響肌肉收縮，在某些情況下會導致心臟衰竭。因此，在某些用途中，它需要在醫生的監護下使用，以便及時處置不良反應。

去氫土根鹼

去氫土根鹼又叫去氫依米丁（Dehydroemetine），是一種合成的抗原蟲藥，其抗阿米巴蟲的特性和結構類似於吐根鹼（僅乙基旁的雙鍵不同），但是它產生的副作用較少。

吐根酚鹼

吐根酚鹼又叫頭九節因（Cephaeline）也是一種在吐根樹根中發現的去甲土根鹼。

蛋白質合成阻斷應用

在實驗室中，通過將吐根鹼二氫氯化水合物與40S亞基核糖體的結合，以阻止真核細胞中蛋白質的合成^[2]。因此，可用於對細胞中蛋白質降解的研究。這種化合物能誘發40S亞基核糖體(S14蛋白)耐吐根鹼突變體發生改變^[3]^[4]，並顯示出具有對小穗苧麻素、異娃兒藤鹼和土布洛素的交叉耐藥性，而非蛋白質合成的其他抑制體^[5]。化合物所誘發突變體所表現出的交叉耐藥性，證明了它們與負責生物活性的吐根鹼共享共同的決定性結構^[6]。

生物合成

生物合成吐根鹼過程

吐根鹼、吐根酚鹼的生物合成主要來自兩種途徑：從酪氨酸合成多巴胺和從牻牛兒焦磷酸（geranyl diphosphate）合成斷馬錢子苷。生物合成開始於多巴胺與斷馬錢子苷反應構成Desacetylipecoside（R型）和Deacetylisoipecoside（S型），然後通過皮克特－施彭格勒反應反應和後續一系列的O-甲基化，去除葡萄糖形成中間體。接下來，中間體與另外的多巴胺分子反應形成7'-O-甲基吐根酚鹼，最終由7'-O-甲基化吐根酚鹼製成吐根酚鹼；由6'-O-甲基吐根鹼製成吐根鹼。^[7]^[8]。

副作用

重度或過度使用吐根鹼可能會引發肌病（myopathy）及心肌症（Cardiomyopathy）的風險。

備註

^ 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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