阿地唑仑

阿地唑仑
臨床資料
给药途径	口服
ATC碼	N05BA07 (WHO) ;
法律規範狀態
法律規範	加：Schedule IV; 德：NpSG; 英：Class C;
藥物動力學數據
药物代谢	肝
生物半衰期	<3小时
排泄途徑	肾
识别信息
	IUPAC命名法 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
PubChem CID	37632;
DrugBank	DB00546 ;
ChemSpider	34519 ;
UNII	KN08449444;
KEGG	D02770 ;
ChEBI	CHEBI:251412 ;
ChEMBL	ChEMBL328250 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID40190611 ;
化学信息
化学式	C19H18ClN5
摩尔质量	351.8
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES Clc3cc2\C(=N/Cc1nnc(n1c2cc3)CN(C)C)c4ccccc4;
	InChI 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 ; Key:GJSLOMWRLALDCT-UHFFFAOYSA-N ;

阿地唑仑（英语：Adinazolam^[1]），商品名Deracyn，是三唑并苯二氮䓬类镇静剂，它是与三唑环融合的苯二氮䓬类。它具有抗焦虑^[2]、抗惊厥、镇静和抗抑郁的特性。^[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]

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、神经错乱和昏迷。^[7]

一项比较阿地唑仑（30毫克和50毫克）与地西泮、劳拉西泮和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]

药效学和药代动力学

阿地唑仑与外周型苯二氮䓬类受体结合，后者作为激动剂与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

^ FR Patent 2248050
^ 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.
^ 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.
^ 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.
^ 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）.
^ 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.
^ Adinazolam. DrugBank. [2023-02-10]. （原始内容存档于2020-02-12）.
^ 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）.
^ 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.
^ ^10.0 ^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.
^ 引用错误：没有为名为FR2的参考文献提供内容
^ 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.
^ 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.

[FR-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.

[antidepressant-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.

[Jackson_B_Hester-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）.

[active_metabolites-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.

[Peng_1984-10] 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.

[FR2-11] 引用错误：没有为名为FR2的参考文献提供内容

[other_metabolites-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.

[Sethy_Francis_Day_1986-13] 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.

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