阿地唑仑

化合物

阿地唑仑英语:Adinazolam[1]),商品名Deracyn,是三唑并苯二氮䓬镇静剂,它是与三唑环融合的苯二氮䓬类。它具有抗焦虑[2]抗惊厥镇静抗抑郁的特性。[3][4]阿地唑仑由杰克逊·海丝特开发,他正在寻求增强阿普唑仑(也是他开发的)的抗抑郁特性。[5]阿地唑仑从未获得FDA批准,也从未在公共市场上销售,但它已作为设计师药物出售。[6]

阿地唑仑
臨床資料
给药途径口服
ATC碼
法律規範狀態
法律規範
藥物動力學數據
药物代谢
生物半衰期<3小时
排泄途徑
识别信息
  • 1-(8-Chloro-6-phenyl-4H-[1,2,4]triazolo[4,5-a][1,4]benzodiazepin-1-yl)-N,N-dimethylmethanamine
CAS号37115-32-5  checkY
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard英语CompTox Chemicals Dashboard (EPA)
化学信息
化学式C19H18ClN5
摩尔质量351.8
3D模型(JSmol英语JSmol
  • Clc3cc2\C(=N/Cc1nnc(n1c2cc3)CN(C)C)c4ccccc4
  • InChI=1S/C19H18ClN5/c1-24(2)12-18-23-22-17-11-21-19(13-6-4-3-5-7-13)15-10-14(20)8-9-16(15)25(17)18/h3-10H,11-12H2,1-2H3 checkY
  • Key:GJSLOMWRLALDCT-UHFFFAOYSA-N checkY

副作用

过量使用该药物可能会造成包括肌肉无力共济失调构音障碍等副作用,尤其是儿童反常兴奋,以及在更严重的情况下可能会导致反射减弱、神经错乱昏迷[7]

一项比较阿地唑仑(30毫克和50毫克)与地西泮劳拉西泮安慰剂的主观影响和滥用可能性的人体研究表明,阿地那唑仑会导致最多的“精神和身体镇静”和最大的“精神不愉快”。[8]

阿地唑仑与外周型苯二氮䓬类受体结合,后者作为激动剂GABA受体发生变构相互作用以产生抑制作用。

代谢

在1984年8月出版的《药学与药理学杂志》中报道阿地那唑仑具有活性代谢物。[9]主要代谢物是N-去甲基阿地唑仑。[10]与其前体相比,N-去甲基阿地唑仑对苯二氮䓬受体的亲和力大约是其前体的25倍,这说明口服给药后会产生类似苯二氮䓬的作用。[11]多次N-脱烷基化导致二甲基氨基甲基侧链的去除,从而造成其效力的差异。[10]其他两种代谢物是α-羟基阿普唑仑和艾司唑仑[12]在1986年8月的同一期刊中,塞西、弗朗西斯和戴依(Day)报道了普罗地芬抑制了N-去甲基阿地唑仑的形成。[13]

参见

参考资料

  1. ^ FR Patent 2248050
  2. ^ Karthik Venkatakrishnan; Lisa L. Von Moltke; Su Xiang Duan; Joseph C. Fleishaker; Richard I. Shader; David J. Greenblat. Kinetic Characterization and Identification of the Enzymes Responsible for the Hepatic Biotransformation of Adinazolam and N-Desmethyladinazolam in Man. Journal of Pharmacy and Pharmacology. March 1998, 50 (3): 265–274. PMID 9600717. S2CID 33656240. doi:10.1111/j.2042-7158.1998.tb06859.x. 
  3. ^ Dunner D, Myers J, Khan A, Avery D, Ishiki D, Pyke R. Adinazolam-A New Antidepressant: Findings of a Placebo-Controlled, Double-Blind Study in Outpatients with Major Depression.. Journal of Clinical Psychopharmacology. June 1998, 7 (3): 170–172. PMID 3298327. doi:10.1097/00004714-198706000-00010. 
  4. ^ Lahti, Robert A.; Vimala H. Sethy; Craig Barsuhn; Jackson B. Hester. Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine.. Neuropharmacology. November 1983, 22 (11): 1277–82. PMID 6320036. S2CID 667962. doi:10.1016/0028-3908(83)90200-9. 
  5. ^ Discovers Award 2004 (PDF). Special Publications. Pharmaceutical Research and Manufacturers of America: 39. April 2004 [August 18, 2006]. (原始内容 (PDF)存档于August 24, 2006). 
  6. ^ Moosmann, Bjoern; Bisel, Philippe; Franz, Florian; Huppertz, Laura M.; Auwärter, Volker. Characterization and in vitro phase I microsomal metabolism of designer benzodiazepines – an update comprising adinazolam, cloniprazepam, fonazepam, 3-hydroxyphenazepam, metizolam, and nitrazolam. Journal of Mass Spectrometry. 2016, 51 (11): 1080–1089. ISSN 1096-9888. PMID 27535017. doi:10.1002/jms.3840. 
  7. ^ Adinazolam. DrugBank. [2023-02-10]. (原始内容存档于2020-02-12). 
  8. ^ M. Bird; D. Katz; M. Orzack; L. Friedman; E. Dessain; B. Beake; J. McEachern; J. Cole. The Abuse Potential of Adinazolam: A Comparison with Diazepam, Lorazepam and Placebo (PDF). NIDA Research Monograph No. 81. 1987 [2015-12-17]. (原始内容 (PDF)存档于2016-12-22). 
  9. ^ Sethy, Vimala H.; R. J. Collins; E. G. Daniels. Determination of biological activity of adinazolam and its metabolites.. Journal of Pharmacy and Pharmacology. August 1984, 36 (8): 546–8. PMID 6148400. S2CID 21094654. doi:10.1111/j.2042-7158.1984.tb04449.x. 
  10. ^ 10.0 10.1 Peng, G. W. Assay of adinazolam in plasma by liquid chromatography. Journal of Pharmaceutical Sciences. August 1984, 73 (8): 1173–5. PMID 6491930. doi:10.1002/jps.2600730840. 
  11. ^ 引用错误:没有为名为FR2的参考文献提供内容
  12. ^ Fraser, A. D.; A. F. Isner; W. Bryan. Urinary screening for adinazolam and its major metabolites by the Emit d.a.u. and FPIA benzodiazepine assays with confirmation by HPLC. Journal of Analytical Toxicology. November–December 1993, 17 (7): 427–31. PMID 8309217. doi:10.1093/jat/17.7.427. 
  13. ^ Sethy, Vimala H.; Jonathan W. Francis; J. S. Day. The effect of proadifen on the metabolism of adinazolam. Journal of Pharmacy and Pharmacology. August 1986, 38 (8): 631–2. PMID 2876087. S2CID 9394686. doi:10.1111/j.2042-7158.1986.tb03099.x.