普瑞巴林

普瑞巴林
(Pregabalin)
临床资料
其他名称	Isobutyl GABA
AHFS/Drugs.com	国际药品名称
MedlinePlus	a605045
核准状况	美 FDA: Pregabalin;
怀孕分级	澳: B3 ; ;
给药途径	口服
ATC码	N03AX16 (WHO) ;
法律规范状态
法律规范	澳：限医生处方（S4）; 加：处方药（℞-only）; 英：处方药（℞-only） (POM); 美：附表V; 处方药（℞-only）;
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
药效起始时间（英语：Onset of action）	1.5 小时
生物半衰期	6.3 小时
排泄途径	肾
识别信息
	IUPAC命名法 (S)-3-(aminomethyl)-5-methylhexanoic acid; ;
CAS号	148553-50-8
PubChem CID	5486971;
DrugBank	DB00230 ;
ChemSpider	4589156 ;
UNII	55JG375S6M;
KEGG	D02716 ;
ChEBI	CHEBI:64356 ;
ChEMBL	ChEMBL1059 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID1045950 ;
ECHA InfoCard	100.119.513
化学信息
化学式	C8H17NO2
摩尔质量	159.23 g.mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES O=C(O)C[C@H](CC(C)C)CN;
	InChI 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 ; Key:AYXYPKUFHZROOJ-ZETCQYMHSA-N ;

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。

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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、镇痛和抗焦虑效果的原因。^[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（K_i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]
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]
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]
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]
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]
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]
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]
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.

外部链接

Pfizer website for Lyrica （页面存档备份，存于互联网档案馆）
U.S. prescribing information （页面存档备份，存于互联网档案馆）
Lyrica Oral at WebMD.com （页面存档备份，存于互联网档案馆）
Erowid Lyrica (Pregabalin) Vault （页面存档备份，存于互联网档案馆）

[emea-spc-1] [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）.

[clevelandclinicmeded.com-2] [2]
Pharmacotherapy Update - Pregabalin (Lyrica®):Part I. [2016-02-22]. （原始内容存档于2017-02-27）.

[3] [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.

[AHFS2015-4] [4]
Pregabalin. The American Society of Health-System Pharmacists. [2015-10-23]. （原始内容存档于2020-08-09）.

[pmid10189176-5] [5]
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.

[Cal2016-6] [6]
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.

[Uch2010-7] [7]
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 .

[pmid16376147-8] [8]
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.

[BenzonRathmell2013-9] [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] [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] [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] [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.

[pmid23642658-13] [13]
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.

[pmid21897498-14] [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] [15]
McMahon SB. Wall and Melzack's textbook of pain 6th. Philadelphia, PA: Elsevier/Saunders. 2013: 515. ISBN 9780702040597.

[pmid17126531-16] [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）.

[EOID-17] [17]
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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