普瑞巴林

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普瑞巴林
化學數據
化學式C8H17NO2
摩爾質量159.23 g·mol−1
識別信息
IUPAC名稱(3S)S)-3-(氨基甲基)-5-甲基己酸
CAS號
PubChem CID

普瑞巴林（Pregabalin），是一種治療癲癇、神經痛、纖維肌痛、廣泛性焦慮症[1][2]的藥物。

藥理學

普瑞巴林是神經遞質γ-氨基丁酸的衍生物，[3] 也是一種強效的加巴噴丁類物質，但它並不與任何γ-氨基丁酸受體結合，而是通過抑制鈣通道發揮作用。[4][5]它是某些電壓依賴性鈣通道（VDCCs）的輔助α2δ亞基位點的配體，從而作為含α2δ亞基的電壓依賴性鈣通道的抑制劑。[4] [6]它與α2δ1以及α2δ2這兩個亞基結合，並在這兩個位點上表現出了相似的親和力，因此普瑞巴林缺乏α2δ亞基的選擇性，[4]但具有電壓依賴性鈣通道的α2δ亞基選擇性。[6] [7] 雖然普瑞巴林不與任何γ-氨基丁酸受體結合，也不會轉換為γ-氨基丁酸或其他γ-氨基丁酸受體激動劑，也不直接調節γ-氨基丁酸的轉運或代謝，[5][6]但它會增加L-穀氨酸脫羧酶（GAD）在大腦中的表達，[8][9] [10] 而此酶是用於合成γ-氨基丁酸的酶，因此可能由於大腦內γ氨基丁酸水平升高造成一些γ-氨基丁酸能的作用。但目前沒有證據可以說明普瑞巴林的作用是除了抑制含α2δ亞基的電壓依賴性鈣通道介導的。[6] [11] 因此，普瑞巴林對其的抑制作用似乎是它抗驚厥、鎮痛和抗焦慮效果的原因。[6][11]


在一項研究中發現，普瑞巴林對含α2δ亞基的電壓依賴性鈣通具有比加巴噴丁高6倍的親和力，[12][13]而在另一項研究中發現，普瑞巴林和加巴噴丁對人類重組α2δ1亞基具有差不多的親和力（Ki分別為32 nM和40 nM）。[14]在任何情況下，普瑞巴林作為鎮痛藥的效力是加巴噴丁的2~4倍，[3][15]在動物身上作為抗驚厥藥時的效力似乎是加巴噴丁的3~10倍。[3][15]

濫用

普瑞巴林因其中樞抑制的特性時常被濫用，通常會使用至少一次300mg或更高的劑量。普瑞巴林在過量時可能具有成癮性和戒斷反應。

參考文獻

  1. ↑ Frampton, JE (September 2014). "Pregabalin: a review of its use in adults with generalized anxiety disorder". CNS Drugs. 28 (9): 835–54. doi:10.1007/s40263-014-0192-0. PMID 25149863.
  2. ↑ "Pregabalin". The American Society of Health-System Pharmacists. Archived from the original on 2020-08-09. Retrieved 2015-10-23. {{cite web}}: Unknown parameter |dead-url= ignored (|url-status= suggested) (help)
  3. ↑ 3.0 3.1 3.2 Bryans JS, Wustrow DJ (March 1999). "3-substituted GABA analogs with central nervous system activity: a review". Medicinal Research Reviews. 19 (2): 149–177. doi:10.1002/(SICI)1098-1128(199903)19:2<149::AID-MED3>3.0.CO;2-B. PMID 10189176. S2CID 38496241.
  4. ↑ 4.0 4.1 4.2 Calandre EP, Rico-Villademoros F, Slim M (November 2016). "Alpha2delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use". Expert Review of Neurotherapeutics. 16 (11): 1263–1277. doi:10.1080/14737175.2016.1202764. PMID 27345098. S2CID 33200190.
  5. ↑ 5.0 5.1 Uchitel OD, Di Guilmi MN, Urbano FJ, Gonzalez-Inchauspe C (2010). "Acute modulation of calcium currents and synaptic transmission by gabapentinoids". Channels. 4 (6): 490–496. doi:10.4161/chan.4.6.12864. PMID 21150315.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 Sills GJ (February 2006). "The mechanisms of action of gabapentin and pregabalin". Current Opinion in Pharmacology. 6 (1): 108–113. doi:10.1016/j.coph.2005.11.003. PMID 16376147.
  7. ↑ Benzon HM, Rathmell JP, Wu CL, Turk DC, Argoff CE, Hurley RW (September 11, 2013). Practical Management of Pain. Elsevier Health Sciences. p. 1006. ISBN 978-0-323-17080-2.
  8. ↑ Lin GQ, You QD, Cheng JF, eds. (August 8, 2011). Chiral Drugs: Chemistry and Biological Action. John Wiley & Sons. p. 88. ISBN 9781118075630. Archived from the original on April 25, 2022. Retrieved August 17, 2016 – via Google Books.
  9. ↑ Li Z, Taylor CP, Weber M, Piechan J, Prior F, Bian F, et al. (September 2011). "Pregabalin is a potent and selective ligand for α(2)δ-1 and α(2)δ-2 calcium channel subunits". European Journal of Pharmacology. 667 (1–3): 80–90. doi:10.1016/j.ejphar.2011.05.054. PMID 21651903. Archived from the original on October 21, 2020. Retrieved October 20, 2020.
  10. ↑ Sze PY (1979). "L-Glutamate Decarboxylase". GABA—Biochemistry and CNS Functions. Advances in Experimental Medicine and Biology. Vol. 123. pp. 59–78. doi:10.1007/978-1-4899-5199-1_4. ISBN 978-1-4899-5201-1. PMID 390996.
  11. ↑ 11.0 11.1 Stahl SM, Porreca F, Taylor CP, Cheung R, Thorpe AJ, Clair A (June 2013). "The diverse therapeutic actions of pregabalin: is a single mechanism responsible for several pharmacological activities?". Trends in Pharmacological Sciences. 34 (6): 332–339. doi:10.1016/j.tips.2013.04.001. PMID 23642658.
  12. ↑ Baidya DK, Agarwal A, Khanna P, Arora MK (July 2011). "Pregabalin in acute and chronic pain". Journal of Anaesthesiology Clinical Pharmacology. 27 (3): 307–314. doi:10.4103/0970-9185.83672. PMC 3161452. PMID 21897498.
  13. ↑ McMahon SB (2013). Wall and Melzack's textbook of pain (6th ed.). Philadelphia, PA: Elsevier/Saunders. p. 515. ISBN 9780702040597.
  14. ↑ Taylor CP, Angelotti T, Fauman E (February 2007). "Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery". Epilepsy Research. 73 (2): 137–150. doi:10.1016/j.eplepsyres.2006.09.008. PMID 17126531. S2CID 54254671. Archived from the original on October 23, 2020. Retrieved October 19, 2020.
  15. ↑ 15.0 15.1 Lauria-Horner BA, Pohl RB (April 2003). "Pregabalin: a new anxiolytic". Expert Opinion on Investigational Drugs. 12 (4): 663–672. doi:10.1517/13543784.12.4.663. PMID 12665421. S2CID 36137322.
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