普瑞巴林

化合物

普瑞巴林(英语:Pregabalin), 是一款被用作治疗癫痫神经性疼痛纤维肌痛广泛性焦虑症[3][4]的药物。

普瑞巴林
(Pregabalin)
临床资料
其他名称Isobutyl GABA
AHFS/Drugs.com国际药品名称
MedlinePlusa605045
核准状况
怀孕分级
给药途径口服
ATC码
法律规范状态
法律规范
药物动力学数据
生物利用度≥90%
血浆蛋白结合率Nil
药物代谢Negligible
代谢产物N-methylpregabalin[1]
药效起始时间英语Onset of action1.5 小时[2]
生物半衰期6.3 小时[2]
排泄途径
识别信息
  • (S)-3-(aminomethyl)-5-methylhexanoic acid
CAS号148553-50-8  checkY
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard英语CompTox Chemicals Dashboard (EPA)
ECHA InfoCard100.119.513 编辑维基数据链接
化学信息
化学式C8H17NO2
摩尔质量159.23 g.mol−1
3D模型(JSmol英语JSmol
  • O=C(O)C[C@H](CC(C)C)CN
  • InChI=1S/C8H17NO2/c1-6(2)3-7(5-9)4-8(10)11/h6-7H,3-5,9H2,1-2H3,(H,10,11)/t7-/m0/s1 checkY
  • Key:AYXYPKUFHZROOJ-ZETCQYMHSA-N checkY

药理学

普瑞巴林是神经递质γ-氨基丁酸的衍生物,[5] 也是种强效的加巴喷丁类化合物,但它并不与任何γ-氨基丁酸受体结合,而是通过抑制钙通道发挥作用。[6][7]它是某些电压依赖性钙通道(VDCCs)的辅助α2δ亚基位点的配体,从而作为含α2δ亚基的电压依赖性钙通道的抑制剂。[6] [8]它与α2δ1以及α2δ2这两个亚基结合,并在这两个位点上表现出了相似的亲和力,因此普瑞巴林缺乏α2δ亚基的选择性,[6]但具有电压依赖性钙通道的α2δ亚基选择性。[8] [9] 虽然普瑞巴林不与任何γ-氨基丁酸受体结合,也不会转换为γ-氨基丁酸或其他γ-氨基丁酸受体激动剂,也不直接调节γ-氨基丁酸的转运或代谢,[7][8]但它会增加L-谷氨酸脱羧酶(GAD)在大脑中的表达[10][11] [12] 而此酶是用于合成γ-氨基丁酸的酶,因此可能由于大脑内γ氨基丁酸水平升高造成一些γ-氨基丁酸能的作用。但目前没有证据可以说明普瑞巴林的作用是除了抑制含α2δ亚基的电压依赖性钙通道介导的。[8] [13] 因此,普瑞巴林对其的抑制作用似乎是它抗惊厥镇痛抗焦虑效果的原因。[8][13]


在一项研究中发现,普瑞巴林对含α2δ亚基的电压依赖性钙通具有比加巴喷丁高6倍的亲和力,[14][15]而在另一项研究中发现,普瑞巴林和加巴喷丁对人类重组α2δ1亚基具有差不多的亲和力(Ki分别为32 nM和40 nM)。[16]在任何情况下,普瑞巴林作为镇痛药的效力是加巴喷丁的2~4倍,[5][17]在动物身上作为抗惊厥药时的效力似乎是加巴喷丁的3~10倍。[5][17]


参考文献

  1. ^ Summary of product characteristics (PDF). European Medicines Agency. 2013-03-06 [2013-05-06]. (原始内容存档 (PDF)于2018-09-16). 
  2. ^ 2.0 2.1 Pharmacotherapy Update - Pregabalin (Lyrica®):Part I. [2016-02-22]. (原始内容存档于2017-02-27). 
  3. ^ Frampton, JE. Pregabalin: a review of its use in adults with generalized anxiety disorder.. CNS Drugs. September 2014, 28 (9): 835–54. PMID 25149863. doi:10.1007/s40263-014-0192-0. 
  4. ^ Pregabalin. The American Society of Health-System Pharmacists. [2015-10-23]. (原始内容存档于2020-08-09). 
  5. ^ 5.0 5.1 5.2 Bryans JS, Wustrow DJ. 3-substituted GABA analogs with central nervous system activity: a review. Medicinal Research Reviews. March 1999, 19 (2): 149–177. PMID 10189176. S2CID 38496241. doi:10.1002/(SICI)1098-1128(199903)19:2<149::AID-MED3>3.0.CO;2-B. 
  6. ^ 6.0 6.1 6.2 Calandre EP, Rico-Villademoros F, Slim M. Alpha2delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use. Expert Review of Neurotherapeutics. November 2016, 16 (11): 1263–1277. PMID 27345098. S2CID 33200190. doi:10.1080/14737175.2016.1202764. 
  7. ^ 7.0 7.1 Uchitel OD, Di Guilmi MN, Urbano FJ, Gonzalez-Inchauspe C. Acute modulation of calcium currents and synaptic transmission by gabapentinoids. Channels. 2010, 4 (6): 490–496. PMID 21150315. doi:10.4161/chan.4.6.12864 . 
  8. ^ 8.0 8.1 8.2 8.3 8.4 Sills GJ. The mechanisms of action of gabapentin and pregabalin. Current Opinion in Pharmacology. February 2006, 6 (1): 108–113. PMID 16376147. doi:10.1016/j.coph.2005.11.003. 
  9. ^ Benzon HM, Rathmell JP, Wu CL, Turk DC, Argoff CE, Hurley RW. Practical Management of Pain. Elsevier Health Sciences. September 11, 2013: 1006. ISBN 978-0-323-17080-2. 
  10. ^ Lin GQ, You QD, Cheng JF (编). Chiral Drugs: Chemistry and Biological Action. John Wiley & Sons. August 8, 2011: 88 [August 17, 2016]. ISBN 9781118075630. (原始内容存档于April 25, 2022) –通过Google Books. 
  11. ^ Li Z, Taylor CP, Weber M, Piechan J, Prior F, Bian F, et al. Pregabalin is a potent and selective ligand for α(2)δ-1 and α(2)δ-2 calcium channel subunits. European Journal of Pharmacology. September 2011, 667 (1–3): 80–90 [October 20, 2020]. PMID 21651903. doi:10.1016/j.ejphar.2011.05.054. (原始内容存档于October 21, 2020). 
  12. ^ Sze PY. L-Glutamate Decarboxylase. GABA—Biochemistry and CNS Functions. Advances in Experimental Medicine and Biology 123. 1979: 59–78. ISBN 978-1-4899-5201-1. PMID 390996. doi:10.1007/978-1-4899-5199-1_4. 
  13. ^ 13.0 13.1 Stahl SM, Porreca F, Taylor CP, Cheung R, Thorpe AJ, Clair A. The diverse therapeutic actions of pregabalin: is a single mechanism responsible for several pharmacological activities?. Trends in Pharmacological Sciences. June 2013, 34 (6): 332–339. PMID 23642658. doi:10.1016/j.tips.2013.04.001. 
  14. ^ Baidya DK, Agarwal A, Khanna P, Arora MK. Pregabalin in acute and chronic pain. Journal of Anaesthesiology Clinical Pharmacology. July 2011, 27 (3): 307–314. PMC 3161452 . PMID 21897498. doi:10.4103/0970-9185.83672 . 
  15. ^ McMahon SB. Wall and Melzack's textbook of pain 6th. Philadelphia, PA: Elsevier/Saunders. 2013: 515. ISBN 9780702040597. 
  16. ^ Taylor CP, Angelotti T, Fauman E. Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Research. February 2007, 73 (2): 137–150 [October 19, 2020]. PMID 17126531. S2CID 54254671. doi:10.1016/j.eplepsyres.2006.09.008. (原始内容存档于October 23, 2020). 
  17. ^ 17.0 17.1 Lauria-Horner BA, Pohl RB. Pregabalin: a new anxiolytic. Expert Opinion on Investigational Drugs. April 2003, 12 (4): 663–672. PMID 12665421. S2CID 36137322. doi:10.1517/13543784.12.4.663. 

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