维基百科

胍法辛

化合物
维基百科中的医学内容仅供参考，并不能视作专业意见。如需获取医疗帮助或意见，请咨询专业人士。详见医学声明。

胍法辛（英语：Guanfacine）以Tenex（速释剂型（immediate-release dosage）和Intuniv（缓释剂型（英语：modified-release dosage））等品牌销售，是一种口服α-2A肾上腺素受体激动剂（英语：Alpha-adrenergic agonist），用于治疗注意力不足过动症(ADHD) 和高血压。[2][3]胍法辛经美国食品药物管理局（FDA）批准用于ADHD的单一疗法，[2]也可用于增强其他药品（例如兴奋剂）的辅助之用。[3]胍法辛也被作仿单标示外使用，用于治疗抽动障碍、焦虑症和创伤后压强综合症 (PTSD)。[4]

胍法辛
临床资料
商品名（英语：Drug nomenclature）Estulic、Intuniv、Tenex及其他。
AHFS/Drugs.comMonograph
MedlinePlusa601059
核准状况
给药途径口服给药
药物类别（英语：Drug class）α-2A肾上腺素受体激动剂（英语：Alpha-adrenergic agonist）
ATC码
法律规范状态
法律规范
识别信息
  • N-(Diaminomethylidene)-2-(2,6-dichlorophenyl)acetamide
CAS号29110-47-2  checkY
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)
ECHA InfoCard100.044.933 编辑维基数据链接
化学信息
化学式C9H9Cl2N3O
摩尔质量246.09 g·mol−1
3D模型（JSmol（英语：JSmol））
  • Clc1cccc(Cl)c1CC(=O)\N=C(/N)N
  • InChI=1S/C9H9Cl2N3O/c10-6-2-1-3-7(11)5(6)4-8(15)14-9(12)13/h1-3H,4H2,(H4,12,13,14,15) checkY
  • Key:INJOMKTZOLKMBF-UHFFFAOYSA-N checkY

使用后常见的副作用有嗜睡、便秘和口干。[3]其他副作用可能有低血压和泌尿系统问题。[5]FDA将胍法辛归类为妊娠期"B类"，表示于动物生殖研究方面尚未证明个体于怀孕或母乳哺育期间对胎儿或婴儿有风险，或是不良影响。[6][5]此药物似乎透过激活大脑中的α-2A肾上腺素受体，减少交感神经系统活动来发挥作用。[3]

胍法辛于1974年首次于文献中被描述，[7]并于1986年在美国被批准用于医疗用途。[3]市面上有这种药品的通用名药物贩售。[3]它是美国于2020年排名第300的最常用处方药，开立的处方笺数量超过100万张。[8][9]

医疗用途

编辑
 
每片为一毫克剂量的胍法辛药片。

胍法辛经FDA批准作为单一疗法，或可联合兴奋剂，用于治疗注意力不足过动症 (ADHD)。[2][10][11]胍法辛被认为无物质滥用潜力（与兴奋剂不同），它甚至可用于降低尼古丁和古柯碱等的滥用问题。[12]此药物也被FDA批准用于治疗高血压。[13]胍法辛可协同增强苯丙胺（安非他命）和哌醋甲酯等兴奋剂在治疗ADHD的作用，且在许多情况下还可帮助控制兴奋剂的副作用。[3]据称胍法辛于治疗ADHD时，可帮助个体更好控制行为、抑制不适当的分心和冲动，并抑制不适当的攻击性冲动。[14]对此药品所做的系统综述和元分析，发现其对于治疗儿童和成人ADHD均有效，在成人治疗中发现效应值适中 (标准化平均差异（Hedges' g） = -0.66)。[15][16][17]有项系统综述和元分析还发现胍法辛可减少患有ADHD的儿童和青少年的对立反抗行为（这些儿童和青少年或者患有，或是不患有对立性反抗症，效应值为小至中等）。[18]但胍法辛和其他α2-肾上腺素受体激动剂被认为在治疗ADHD的有效性方面不如兴奋剂。[18][19][17]

胍法辛也被用于治疗抽动障碍、焦虑症（如广泛性焦虑症）和创伤后压强综合症（PTSD）。[4]胍法辛和其他α2A-肾上腺素受体激动剂具有抗焦虑药般的作用，[20]可减少杏仁核产生的情绪反应，并加强前额叶皮质对情绪、行动和思想的调节。[21]这些作用源自于对心理压强诱导的儿茶酚胺释放的抑制，以及前额叶皮质中受体侧突触的作用。[21]由于其生物半衰期时间较长，也可改善PTSD患者因做噩梦而导致的睡眠中断。[22]所有这些行为都可能有助于缓解与PTSD相关的过度警觉、创伤记忆重现和冲动。[23]胍法辛似乎对治疗遭受心理创伤或受虐待儿童特别有帮助。[21]

不良影响

编辑

胍法辛的副作用是有剂量曝露-反应相关性（英语：Dose–response relationship）。[24]

很常见（>10%发生率）的不良反应有嗜睡、疲倦、头痛和腹痛。[25]

常见（发生率1-10%）不良反应有厌食、恶心、口干、尿失禁和皮疹。[25]

根据报告，胍法辛会导致罹患ADHD儿童有很高的嗜睡率，例如在一项试验中，服用胍法辛组的嗜睡率为73%，服用安慰剂组为6%。[26][27]

胍法辛可能会导致罹患ADHD的儿童睡眠恶化，包括减少总睡眠时间。[26][27]

于2020年所做的一项系统综述发现胍法辛产生的副作用有腹痛、镇静和QT间期延长（英语：Drug-induced QT prolongation）。[28]

交互作用

编辑

胍法辛的利用率受CYP3A4和CYP3A5（英语：CYP3A5）两种酵素的显著影响。抑制或诱导这些酵素的药物会改变胍法辛于循环中的数量，因而改变其功效和不良反应发生率。由于其对心脏有影响，若与其他循环系统活性药物一起使用时应谨慎。当它与镇静剂一起使用时，也应谨慎。[25]

药理学

编辑

药效学

编辑
胍法辛[29]
结合位点 亲和力(纳摩尔（nM）) 物种 参考
α-2A肾上腺素受体 50.3 – 93.3 人类 [30][31]
α-2B肾上腺素受体 1,020 – 1,380 人类 [30][31]
α-2C肾上腺素受体 1,120 – 3,890 人类 [30][31]
数值越小，与结合位点亲和力越强。

胍法辛是α-2A肾上腺素受体的高度结合选择性（英语：binding selectivity）激动剂，对其他受体的结合亲和力较低。[29]然而它也是一种5-HT2B受体激动剂。[32][33][34][35]

胍法辛透过活化中枢神经系统内的α2A-肾上腺素受体[36]而发挥作用。导致周围神经系统流出减少，而降低外周交感神经张力，从而降低血管的心脏收缩压和舒张（英语：dystole）压。[37]

胍法辛在治疗ADHD时，被认为是透过加强前额叶皮质对注意力和行为的调节来发挥作用。[38][14]这些对前额叶皮质功能的增强作用被认为是由于药物刺激树突上的受体侧突触α2A-肾上腺素受体，而非依赖释放侧突触α2A-肾上腺素受体的活化。[14]环磷酸鸟苷（cAMP）介导的HCN通道（英语：HCN channel）和KCNQ通道（英语：KCNQ channels）开放受到抑制，而增强前额叶皮质突触连接和神经元动作电位发生。[38][39]在猴子身上的实验结果，发现胍法辛可改善工作记忆、注意力调节和行为抑制，而这些作用与其镇静作用无关。[14]使用胍法辛治疗前额叶疾患是由耶鲁大学医学院阿恩斯滕实验室（Arnsten Lab）所开发。[38][14]

胍法辛对α2A-肾上腺素受体的选择性比可乐定高很多，可乐定不仅能结合及活化α2A肾上腺素受体，还能结合及活化α2B和α2C肾上腺素受体以及咪唑啉受体（英语：Imidazoline receptor）。[14]此药品在降低血压和镇静方面比可乐定为弱，对受体侧突触的α2A肾上腺素受体的作用也比可乐定为弱（降低蓝斑核活性和正肾上腺素释放的效果低10倍），并且在释放侧突触的α2A肾上腺素受体方面可能具有更大的功效（由胍法辛比可乐定更能增强老年猴子的前额皮质相关工作记忆所显示）。[14]

5-HT2B受体被活化后是众人已知的抗标靶，与心脏瓣膜疾病（英语：Valvular heart disease）有关联。[32][33]然而并非所有5-HT2B受体激动剂（例如罗平尼咯）都具有这种作用。[32][33]虽然胍法辛已被使用许久，但并无与心脏瓣膜疾病相关的报导，可能是其对5-HT2B受体有较小的激动效力。[35][40][41]在体外研究中，其对5-HT2B受体的亲和力比对α2A肾上腺素受体的亲和力低100倍，对5-HT2B受体的亲和力比血清素低30倍，而在活化5-HT2B受体的效力比对血清素低1,000倍。[40]结论是在临床性浓度下，胍法辛预计不会表现出与5-HT2B受体的显著结合或激活，因此不太可能是人类的心脏瓣膜疾病的病原体。[40]但仍有不同的研究提出胍法辛在5-HT2B受体激动方面具有不同程度功效的报告，[34][35][40][41]截至2018年，尚无关于胍法辛导致心脏瓣膜疾病风险的临床数据。[42]虽说胍法辛于此的可能性较低，但仍可能存有风险。[40]

药物动力学

编辑

口服胍法辛的生物利用度为80%。没明确的证据表明存在任何首过代谢。其生物半衰期为17小时，主要消除途径为肾脏。主要代谢产物是3-羟基化衍生物，具有中等生物转化的证据，关键中间体是环氧化合物。[43]肾功能受损患者的消除过程未受影响。因此对此类患者而言，有经过肝脏代谢的假设，此类患者产生姿位性低血压和镇静等副作用频率增加也证明此点。[44]

历史

编辑

胍法辛于1974年首次经文献描述，[7][45][46][47][48]于1986年被FDA核准用于治疗高血压，商品名为Tenex。[49]接着于2010年被FDA批准用于治疗6至17岁族群的ADHD。[10]它于2015年被欧洲药品管理局批准用于治疗ADHD，商品名为Intuniv。[50]此药品于2018年被加入澳大利亚药品福利计划（英语：Pharmaceutical Benefits Scheme）中，用于治疗ADHD。[51]

社会与文化

编辑

品牌名称

编辑

此药品的品牌名称有Tenex（速释剂型）、Afken、Estulic和Intuniv（缓释剂型）。

药品研究

编辑

胍法辛已被研究作为治疗PTSD用。对成人的疗效证据有限，但一项研究发现对同时罹患ADHD的儿童有积极的结果。[52]此药物对于使用选择性5-羟色胺再摄取抑制剂 (SSRI) 治疗无反应的成年PTSD患者也可能有用。[53]

使用胍法辛治疗妥瑞症的研究结果是好坏参半。[54]

胍法辛似乎不能有效改善患有ADHD和行为性失眠的儿童的睡眠。[26]反而是此药品在一项临床试验中会让某些睡眠参数恶化（例如总睡眠时间）。[26][27]

胍法辛已被研究用于治疗类阿片药物、乙醇和尼古丁的戒断，[55]已被证明有助于减少试图戒烟者因压强所引起对尼古丁的渴望，这可能涉及加强前额叶皮质介导的自我控制。[56]

胍法辛已被研究用于治疗影响前额叶皮质功能相关的各种疾病，包括脑外伤、中风、思觉失调和老年人的认知和注意力问题。[14][57]

目前有研究使用胍法辛作治疗COVID19后综合症之用。[58][59][60]

参见

编辑
  1. ^ Prescription medicines: registration of new chemical entities in Australia, 2017. Therapeutic Goods Administration (TGA). 2022-06-21 [2023-04-09]. （原始内容存档于2023-04-10）. 
  2. ^ 2.0 2.1 2.2 2.3 Intuniv- guanfacine tablet, extended release Intuniv- guanfacine kit. DailyMed. 2021-01-26 [2022-08-06]. （原始内容存档于2022-08-06）. 
  3. ^ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Guanfacine Monograph for Professionals. Drugs.com. American Society of Health-System Pharmacists. [2019-03-18]. （原始内容存档于2018-01-15） （英语）. 
  4. ^ 4.0 4.1 Boland RJ, Verduin ML, Sadock BJ. Ruiz P , 编. Kaplan & Sadock's Concise Textbook of Clinical Psychiatry 5th. Philadelphia. 2023: 1811–1812 [2023-01-12]. ISBN 978-1-9751-6748-6. OCLC 1264172789. （原始内容存档于2023-02-08）. 
  5. ^ 5.0 5.1 British national formulary: BNF 76 76. Pharmaceutical Press. 2018: 349–350. ISBN 9780857113382. 
  6. ^ Patient Information. INTUNIV (in-TOO-niv) (guanfacine). Extended-Release Tablets (PDF). FDA.gov. [2022-10-12]. （原始内容存档 (PDF)于2022-10-13）. 
  7. ^ 7.0 7.1 Turner, A. S. (1974). BS 100-141 in the treatment of arterial hypertension. Seventh World Congr. of Cardiol., Abstr, 336.
  8. ^ The Top 300 of 2020. ClinCalc. [2022-10-07]. （原始内容存档于2021-01-12）. 
  9. ^ Guanfacine - Drug Usage Statistics. ClinCalc. [2022-10-07]. （原始内容存档于2020-07-08）. 
  10. ^ 10.0 10.1 Kornfield R, Watson S, Higashi AS, Conti RM, Dusetzina SB, Garfield CF, Dorsey ER, Huskamp HA, Alexander GC. Effects of FDA advisories on the pharmacologic treatment of ADHD, 2004-2008. Psychiatric Services. April 2013, 64 (4): 339–346. PMC 4023684  . PMID 23318985. doi:10.1176/appi.ps.201200147. 
  11. ^ Zito JM, Derivan AT, Kratochvil CJ, Safer DJ, Fegert JM, Greenhill LL. Off-label psychopharmacologic prescribing for children: history supports close clinical monitoring. Child and Adolescent Psychiatry and Mental Health //www.ncbi.nlm.nih.gov/pmc/articles/PMC2566553 |PMC=缺少标题 (帮助). September 2008, 2 (1): 24. PMC 2566553  . PMID 18793403. doi:10.1186/1753-2000-2-24  . 
  12. ^ Clemow, DB; Walker, DJ. The potential for misuse and abuse of medications in ADHD: a review.. Postgraduate Medicine. September 2014, 126 (5): 64–81. PMID 25295651. S2CID 207580823. doi:10.3810/pgm.2014.09.2801. 
  13. ^ guanfacine (Rx) - Intuniv, Tenex. Medscape Reference. WebMD. [2013-11-09]. （原始内容存档于2019-05-18）. 
  14. ^ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 14.7 Arnsten AF, Jin LE. Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale. The Yale Journal of Biology and Medicine. March 2012, 85 (1): 45–58. PMC 3313539  . PMID 22461743. 
  15. ^ Radonjić NV, Bellato A, Khoury NM, Cortese S, Faraone SV. Nonstimulant Medications for Attention-Deficit/Hyperactivity Disorder (ADHD) in Adults: Systematic Review and Meta-analysis. CNS Drugs. May 2023, 37 (5): 381–397. PMID 37166701. S2CID 258616507. doi:10.1007/s40263-023-01005-8. 
  16. ^ Yu S, Shen S, Tao M. Guanfacine for the Treatment of Attention-Deficit Hyperactivity Disorder: An Updated Systematic Review and Meta-Analysis. J Child Adolesc Psychopharmacol. March 2023, 33 (2): 40–50. PMID 36944092. S2CID 257664282. doi:10.1089/cap.2022.0038. 
  17. ^ 17.0 17.1 Catalá-López F, Hutton B, Núñez-Beltrán A, Page MJ, Ridao M, Macías Saint-Gerons D, Catalá MA, Tabarés-Seisdedos R, Moher D. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials. PLOS ONE. 2017, 12 (7): e0180355. Bibcode:2017PLoSO..1280355C. PMC 5507500  . PMID 28700715. doi:10.1371/journal.pone.0180355  . 
  18. ^ 18.0 18.1 Pringsheim T, Hirsch L, Gardner D, Gorman DA. The pharmacological management of oppositional behaviour, conduct problems, and aggression in children and adolescents with attention-deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder: a systematic review and meta-analysis. Part 1: psychostimulants, alpha-2 agonists, and atomoxetine. Can J Psychiatry. February 2015, 60 (2): 42–51. PMC 4344946  . PMID 25886655. doi:10.1177/070674371506000202. 
  19. ^ Padilha SC, Virtuoso S, Tonin FS, Borba HH, Pontarolo R. Efficacy and safety of drugs for attention deficit hyperactivity disorder in children and adolescents: a network meta-analysis. Eur Child Adolesc Psychiatry. October 2018, 27 (10): 1335–1345. PMID 29460165. S2CID 3402756. doi:10.1007/s00787-018-1125-0. 
  20. ^ Morrow BA, George TP, Roth RH. Noradrenergic alpha-2 agonists have anxiolytic-like actions on stress-related behavior and mesoprefrontal dopamine biochemistry. Brain Research. November 2004, 1027 (1–2): 173–178. PMID 15494168. S2CID 7066842. doi:10.1016/j.brainres.2004.08.057. 
  21. ^ 21.0 21.1 21.2 Arnsten AF, Raskind MA, Taylor FB, Connor DF. The Effects of Stress Exposure on Prefrontal Cortex: Translating Basic Research into Successful Treatments for Post-Traumatic Stress Disorder. Neurobiology of Stress. January 2015, 1: 89–99. PMC 4244027  . PMID 25436222. doi:10.1016/j.ynstr.2014.10.002. 
  22. ^ Kozaric-Kovacic D. Psychopharmacotherapy of posttraumatic stress disorder. Croatian Medical Journal. August 2008, 49 (4): 459–475. PMC 2525822  . PMID 18716993. doi:10.3325/cmj.2008.4.459. 
  23. ^ Kaminer D, Seedat S, Stein DJ. Post-traumatic stress disorder in children. World Psychiatry. June 2005, 4 (2): 121–125. PMC 1414752  . PMID 16633528. 
  24. ^ Jerie P. Clinical experience with guanfacine in long-term treatment of hypertension. Part II: adverse reactions to guanfacine. British Journal of Clinical Pharmacology. 1980, 10 (Suppl 1): 157S–164S. PMC 1430125  . PMID 6994770. doi:10.1111/j.1365-2125.1980.tb04924.x. 
  25. ^ 25.0 25.1 25.2 Intuniv 1 mg, 2 mg, 3 mg, 4 mg prolonged-release tablets - Summary of Product Characteristics. UK Electronic Medicines Compendium. June 2017 [2017-07-07]. （原始内容存档于2018-01-15）. 
  26. ^ 26.0 26.1 26.2 26.3 Anand S, Tong H, Besag FM, Chan EW, Cortese S, Wong IC. Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment. Paediatr Drugs. June 2017, 19 (3): 235–250 [2024-02-22]. PMID 28391425. S2CID 2220464. doi:10.1007/s40272-017-0224-6. （原始内容存档于2024-02-22）. 
  27. ^ 27.0 27.1 27.2 Rugino TA. Effect on Primary Sleep Disorders When Children With ADHD Are Administered Guanfacine Extended Release. J Atten Disord. January 2018, 22 (1): 14–24. PMID 25376194. S2CID 22675882. doi:10.1177/1087054714554932. 
  28. ^ Solmi M, Fornaro M, Ostinelli EG, Zangani C, Croatto G, Monaco F, Krinitski D, Fusar-Poli P, Correll CU. Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects. World Psychiatry. June 2020, 19 (2): 214–232. PMC 7215080  . PMID 32394557. doi:10.1002/wps.20765. 
  29. ^ 29.0 29.1 Roth BL, Driscol J. PDSP Ki Database. Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. 2011-01-12 [2013-11-15]. （原始内容存档于2013-11-08）. 
  30. ^ 30.0 30.1 30.2 Jasper JR, Lesnick JD, Chang LK, Yamanishi SS, Chang TK, Hsu SA, et al. Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding. Biochemical Pharmacology. April 1998, 55 (7): 1035–1043. PMID 9605427. doi:10.1016/s0006-2952(97)00631-x. 
  31. ^ 31.0 31.1 31.2 Uhlén S, Porter AC, Neubig RR. The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors. The Journal of Pharmacology and Experimental Therapeutics. December 1994, 271 (3): 1558–1565. PMID 7996470. 
  32. ^ 32.0 32.1 32.2 Bender AM, Parr LC, Livingston WB, Lindsley CW, Merryman WD. 2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery. J Med Chem. August 2023, 66 (16): 11027–11039. PMID 37584406. S2CID 260924858. doi:10.1021/acs.jmedchem.3c01178. These results strongly indicate substantial risks for treatments involving 5-HT2B agonists, and it has been recommended that all serotonergic drugs be screened for this functional profile.43,59 [...] Additionally, there are cases of marketed drugs that were only later determined to have 5-HT2B activity. Of particular note is guanfacine, an FDA-approved medication for the treatment of attention deficit hyperactivity disorder (ADHD) that possesses potent 5-HT2B agonist activity in functional readouts to a similar degree as known valvulopathogens.66 
  33. ^ 33.0 33.1 33.2 Hutcheson JD, Setola V, Roth BL, Merryman WD. Serotonin receptors and heart valve disease--it was meant 2B. Pharmacol Ther. November 2011, 132 (2): 146–57. PMC 3179857  . PMID 21440001. doi:10.1016/j.pharmthera.2011.03.008. 
  34. ^ 34.0 34.1 Huang XP, Setola V, Yadav PN, Allen JA, Rogan SC, Hanson BJ, Revankar C, Robers M, Doucette C, Roth BL. Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment. Molecular Pharmacology. October 2009, 76 (4): 710–722. PMC 2769050  . PMID 19570945. doi:10.1124/mol.109.058057. 
  35. ^ 35.0 35.1 35.2 Unett DJ, Gatlin J, Anthony TL, Buzard DJ, Chang S, Chen C, Chen X, Dang HT, Frazer J, Le MK, Sadeque AJ, Xing C, Gaidarov I. Kinetics of 5-HT2B receptor signaling: profound agonist-dependent effects on signaling onset and duration. J Pharmacol Exp Ther. December 2013, 347 (3): 645–59. PMID 24049061. S2CID 8013309. doi:10.1124/jpet.113.207670. 
  36. ^ Tardner, Paul. A Comprehensive Literature Review on Guanfacine as a Potential Treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). International Journal of Environmental Science and Technology. May 2023 [2024-02-22]. （原始内容存档于2023-09-21）. 
  37. ^ van Zwieten PA, Timmermans PB. Centrally mediated hypotensive activity of B-HT 933 upon infusion via the cat's vertebral artery. Pharmacology. 1983, 21 (5): 327–332. PMC 1427667  . PMID 7433512. doi:10.1111/j.1365-2125.1983.tb00311.x. 
  38. ^ 38.0 38.1 38.2 Arnsten AF. The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Review of Neurotherapeutics. October 2010, 10 (10): 1595–1605. PMC 3143019  . PMID 20925474. doi:10.1586/ern.10.133. 
  39. ^ Wang M, Ramos BP, Paspalas CD, Shu Y, Simen A, Duque A, Vijayraghavan S, Brennan A, Dudley A, Nou E, Mazer JA, McCormick DA, Arnsten AF. Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex. Cell. April 2007, 129 (2): 397–410. PMID 17448997. S2CID 741677. doi:10.1016/j.cell.2007.03.015  . 
  40. ^ 40.0 40.1 40.2 40.3 40.4 Therapeutic Goods Administration. Australian Public Assessment Report for Guanfacine (as hydrochloride) (PDF). May 2018 [2024-02-22]. （原始内容存档 (PDF)于2024-01-18）. 
  41. ^ 41.0 41.1 Roihuvuo, E. (2022). Classical psychedelics and NBOMes as serotonin 2B receptor agonists: Valvulopathogenic signaling pathways and cardiac safety concerns (Master's thesis, Itä-Suomen yliopisto). http://urn.fi/urn:nbn:fi:uef-20220118 （页面存档备份，存于互联网档案馆）
  42. ^ Mladěnka P, Applová L, Patočka J, Costa VM, Remiao F, Pourová J, Mladěnka A, Karlíčková J, Jahodář L, Vopršalová M, Varner KJ, Štěrba M. Comprehensive review of cardiovascular toxicity of drugs and related agents. Med Res Rev. July 2018, 38 (4): 1332–1403. PMC 6033155  . PMID 29315692. doi:10.1002/med.21476. The list of valvulopathic drugs is short and can be seen in Table 7. According to a recent analysis, other drugs, in particular guanfacine, might possess some risk, but clinical data are yet not available.368–370 
  43. ^ Kiechel JR. Pharmacokinetics and metabolism of guanfacine in man: a review. British Journal of Clinical Pharmacology. 1980, 10 (Suppl 1): 25S–32S. PMC 1430131  . PMID 6994775. doi:10.1111/j.1365-2125.1980.tb04901.x. 
  44. ^ Kirch W, Köhler H, Braun W. Elimination of guanfacine in patients with normal and impaired renal function. British Journal of Clinical Pharmacology. 1980, 10 (Suppl 1): 33S–35S. PMC 1430110  . PMID 6994776. doi:10.1111/j.1365-2125.1980.tb04902.x. 
  45. ^ Scholtysik G. Proceedings: Inhibition of effects of accelerator nerve stimulation in cats and rabbits by BS 100-141 and guanabenz. Naunyn Schmiedebergs Arch Pharmacol. 1974, 282 (Suppl): suppl 282:R86. PMID 4276642. 
  46. ^ Bream JB, Lauener H, Picard CW, Scholtysik G, White TG. Substituted phenylacetylguanidines: a new class of antihypertensive agents. Arzneimittelforschung. October 1975, 25 (10): 1477–82. PMID 1243024. 
  47. ^ Saameli K, Scholtysik G, Waite R. Pharmacology of BS 100-141, a centrally acting antihypertensive drug. Clin Exp Pharmacol Physiol. 1975,. Suppl 2: 207–12. PMID 241524. 
  48. ^ Dubach UC, Huwyler R, Radielovic P, Singeisen M. A new centrally action antihypertensive agent guanfacine (BS 100-141). Arzneimittelforschung. 1977, 27 (3): 674–6. PMID 326262. 
  49. ^ Drugs@FDA: FDA-Approved Drugs. [2024-02-22]. （原始内容存档于2017-06-29）. 
  50. ^ European Medicines Agency: Intuniv. Europa (web portal). October 2015 [2016-02-03]. （原始内容存档于2018-08-16）. 
  51. ^ New drugs listed on the PBS for rheumatoid arthritis, cystic fibrosis and ADHD. Royal Australian College of General Practitioners. [2018-09-11]. （原始内容存档于2018-09-11）. 
  52. ^ Connor DF, Grasso DJ, Slivinsky MD, Pearson GS, Banga A. An open-label study of guanfacine extended release for traumatic stress related symptoms in children and adolescents. Journal of Child and Adolescent Psychopharmacology. May 2013, 23 (4): 244–251. PMC 3657282  . PMID 23683139. doi:10.1089/cap.2012.0119. 
  53. ^ Belkin MR, Schwartz TL. Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder. Drugs in Context. 2015, 4: 212286. PMC 4544272  . PMID 26322115. doi:10.7573/dic.212286. 
  54. ^ Srour M, Lespérance P, Richer F, Chouinard S. Psychopharmacology of tic disorders. Journal of the Canadian Academy of Child and Adolescent Psychiatry. August 2008, 17 (3): 150–159. PMC 2527768  . PMID 18769586. 
  55. ^ Sofuoglu M, Sewell RA. Norepinephrine and stimulant addiction. Addiction Biology. April 2009, 14 (2): 119–129. PMC 2657197  . PMID 18811678. doi:10.1111/j.1369-1600.2008.00138.x. 
  56. ^ McKee SA, Potenza MN, Kober H, Sofuoglu M, Arnsten AF, Picciotto MR, Weinberger AH, Ashare R, Sinha R. A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation. Journal of Psychopharmacology. March 2015, 29 (3): 300–311. PMC 4376109  . PMID 25516371. doi:10.1177/0269881114562091. 
  57. ^ Arnsten AF. Guanfacine's mechanism of action in treating prefrontal cortical disorders: Successful translation across species. Neurobiol Learn Mem. December 2020, 176: 107327. PMC 7567669  . PMID 33075480. doi:10.1016/j.nlm.2020.107327. 
  58. ^ Fesharaki Zadeh A, Arnsten AF, Wang M. Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID. Neurol Int. May 2023, 15 (2): 725–742. PMC 10303664  . PMID 37368329. doi:10.3390/neurolint15020045  . 
  59. ^ Arnsten AF, Ishizawa Y, Xie Z. Scientific rationale for the use of α2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. April 2023: 1–13. PMC 10080530  . PMID 37029295. doi:10.1038/s41380-023-02057-4. 
  60. ^ Fesharaki-Zadeh, Arman; Lowe, Naomi; Arnsten, Amy F.T. Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in "Long-COVID19". Neuroimmunology Reports. 2023, 3: 100154. PMC 9691274  . doi:10.1016/j.nerep.2022.100154. 

#invoke:navbox

检索自“https://zh.wikipedia.org/w/index.php?title=胍法辛&oldid=83078414”