盐酸丁二胍

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盐酸丁二胍
别名 N-Butylimidocarbonimidic diamide[來源請求]
识别
CAS号 692-13-7
PubChem 2468
ChemSpider 2374
SMILES
EINECS 211-726-4
DrugBank DB04830
KEGG D00595
MeSH Buformin
ATC代码 A10BA03
性质
化学式 C6H15N5
摩尔质量 157.22 g·mol−1
log P -1.2[1]
药理学
给药途径 口服
排泄 肾脏
相关物质
相关化学品
若非注明,所有数据均出自一般条件(25 ℃,100 kPa)下。

丁二胍 又名丁双胍,药品名"丁福明"是一种口服降糖药,主要用于二型糖尿病的治疗,与二甲双胍,苯乙双胍同属于双胍类口服降糖药.

化学性质与动物毒性[编辑]

盐酸丁二胍是白色或黄色, 无味, 晶体粉末, 入口有弱酸苦味. 熔点 174 到 177°C, 为强碱, 可溶于水, 甲醇, 乙醇, 不溶于氯仿和醚类.[2][3] 毒性: 豚鼠 LD50 皮下 18 毫克/公斤; 小鼠 LD50 腹腔内 140 毫克/公斤 口服 300 毫克/公斤 .[4] 分配系数 (log P 辛醇-水) -1.20E+00; 水溶性在25°C为 7.46E+05 毫克/升. 蒸汽压 于25°C 为 1.64E-04 毫米汞柱 (估计值).

作用机理[编辑]

盐酸丁二胍能够延迟肠胃途径的糖吸收, 增加胰岛素敏感性和细胞的糖摄入, 并且抑制肝糖合成. 盐酸丁二胍和其他双胍类口服降糖药一样, 不是以直接降血糖为主要作用机理, 而是对抗血糖水平过高. 服用不会产生低血糖的现象, 但能够有效降低糖尿病人的空腹与餐后血糖..[5]

药物动力学[编辑]

剂量[编辑]

日常给药剂量为 150–300 毫克 口服.[6]

副作用与用药禁忌[编辑]

常见副作用为食欲匮乏, 恶心, 腹泻, 口中有金属异味和体重减轻. 有糖尿病昏迷, 酮症酸中毒, 严重感染, 严重创伤者禁用.

毒性[编辑]

盐酸丁二胍由于可能导致乳酸堆积的可能性增加在一些国家被退市. 目前在罗马尼亚, 匈牙利, 台湾和日本仍作为处方药被应用. [7][8][9][10][11][12] 乳酸堆积症一般只在盐酸丁二胍血浆浓度超过的 0.60 微克/毫升的病人中发生, 在肾功能正常的患者中十分罕见.[13][14][15]

抗癌作用[编辑]

盐酸丁二胍和二甲双胍还有苯乙双胍一样, 抑制癌细胞生长和发育[16][17][18][19][20] 其抗癌机制是由于其可以阻断瓦氏效应并且将癌细胞的供能途径从细胞基质糖解逆转回依靠线粒体的丙酮酸途径.[21] [22]

历史[编辑]

盐酸丁二胍于1957年被作为降糖药合成.[23]

参考文献[编辑]

  1. ^ F. Macdonald. Dictionary of pharmacological agents: Volumes 1-2 - Page 344, 1997
  2. ^ Jacker HJ. [New Pharmacologic Products. 2. Buformin For Oral Therapy Of Diabetes]. Pharm Prax. 1964;10:247-9.
  3. ^ Eustace George Coverly Clarke, Judith Berle, Pharmaceutical Society of Great Britain. Dept. of Pharmaceutical Sciences. Isolation and identification of drugs in pharmaceuticals, body fluids and post-mortem material, Volume 1. Pharmaceutical Press 1974, p226
  4. ^ Shroff JR, Bandurco V, Desai R, Kobrin S, Cervoni P. Chemistry and hypoglycemic activity of benzimidoylpyrazoles. J Med Chem 1981 Dec;24(12):1521-5.
  5. ^ Enrique Ravina, Hugo Kubinyi. The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. Wiley. 2011 p 215
  6. ^ Gustav Kuschinsky, Heinz Lüllmann. Textbook of pharmacology. Academic Press p 225, 1973
  7. ^ Hankó B, Tukarcs E, Kumli P, Vincze Z. Antidiabetic drug utilization in Hungary. Pharm World Sci. 2005 Jun;27(3):263-5.
  8. ^ Hankó BZ, Reszegi CA, Kumli P, Vincze Z. [Practice of antidiabetic therapy in Hungary]. Acta Pharm Hung. 2005;75(2):77-86.
  9. ^ Jerry L. Schlesser, Gale Research Inc. Drugs available abroad. Derwent Publications, Ltd - 1990 p28
  10. ^ Verdonck L, Sangster B, van Heijst A, de Groot G, Maes R. Buformin concentrations in a case of fatal lactic acidosis. Diabetologia. 1981年, 20 (1): 45–6. doi:10.1007/BF01789112. PMID 7202882. 
  11. ^ Chou CH, Cheng CL, Huang CC. A validated HPLC method with ultraviolet detection for the determination of buformin in plasma. Biomed Chromatogr. 2004 May;18(4):254-8.
  12. ^ Takeda Announces Submission Of Application For Additional Indication Of Actos In Japan; Concomitant Therapy With Biguanides For Type 2 Diabetes. Medical News Today. 28 Jan 2007
  13. ^ Wittmann P, Haslbeck M, Bachmann W, Mehnert H. [Lactic acidosis in diabetics on biguanides (author's translation)] Deutsche Medizinische Wochenschrift 102(1):5-10, 1977
  14. ^ Berger W, Mehnert-Aner S, Mülly K, Heierli C, Ritz R. [10 cases of lactic acidosis during biguanide therapy (buformin and phenformin)]. Schweizerische medizinische Wochenschrift. 106:1830-1834, 1976
  15. ^ Deppermann D, Heidland A, Ritz E, Hörl W. [Lactic acidosis--a possible complication in buformin-treated diabetics (author's transl)]. Klin Wochenschr. 1978年, 56 (17): 843–53. PMID 713413. 
  16. ^ Sakae Saito, Aki Furuno, Junko Sakurai, Asami Sakamoto, Hae-Ryong Park, Kazuo Shin-ya, Takashi Tsuruo, and Akihiro Tomida. Chemical Genomics Identifies the Unfolded Protein Response as a Target for Selective Cancer Cell Killing during Glucose Deprivation. Cancer Research 2009;69(10):4225–34
  17. ^ Vladimir N. Anisimov. Insulin/IGF-1 signaling pathway driving aging and cancer as a target for pharmacological intervention. Experimental Gerontology Volume 38, Issue 10, October 2003, Pages 1041-1049
  18. ^ Valery A. Alexandrov, Vladimir N. Anisimov, Natalia M. Belous, Inna A. Vasilyeva and Vera B. Mazon. The inhibition of the transplacental blastomogenic effect of nitrosomethylurea by postnatal administration of buformin to rats. Carcinogenesis Volume 1, Issue 12 Pp. 975-978, 1980
  19. ^ Anisimov VN, Ostroumova MN, Dil'man VM. Inhibition of the blastomogenic effect of 7,12-dimethylbenz(a)anthracene in female rats by buformin, diphenin, a polypeptide pineal extract and L-DOPA. Bulletin of Experimental Biology and Medicine. Volume 89, Number 6, 819-822, 1980
  20. ^ Vladimir N. Anisimov, Lev M. Berstein, Irina G. Popovich, Mark A. Zabezhinski, Peter A. Egormin, Margarita L. Tyndyk, Ivan V. Anikin, Anna V. Semenchenko, Anatoli I. Yashin. Central and Peripheral Effects of Insulin/IGF-1 Signaling in Aging and Cancer: Antidiabetic Drugs as Geroprotectors and Anticarcinogens. Annals of the New York Academy of Sciences. 1057:220-234, 2005
  21. ^ Matthew G. Vander Heiden, Lewis C. Cantley, and Craig B. Thompson. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science 324 (5930): 1029-1033, 2009.
  22. ^ Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, Montminy M, Cantley LC. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005 Dec 9;310(5754):1642-6.
  23. ^ Seymour L. Shapiro et al. Salts Of N-Amylbiguanide. US Patent number: 2961377; Filing date: Aug 5, 1957; Issue date: 1960