Gabapentinoids are 3-substituted derivatives of the neurotransmitter γ-aminobutyric acid (GABA) which block α2δ subunit-containing voltage-dependent calcium channels (VDCCs).[1][2] Clinically-used gabapentinoids include gabapentin (Neurontin) and pregabalin (Lyrica),[1][2] as well as a gabapentin prodrug, gabapentin enacarbil (Horizant).[3] Another analogue mirogabalin is in clinical trials but has not yet been approved.[4] Other compounds from this family used in research but not developed for medical use include atagabalin, 4-methylpregabalin and PD-217,014. Gabapentinoids are used clinically in the treatment of conditions including epilepsy, neuropathic pain, fibromyalgia, anxiety, and restless legs syndrome, among others.[1][5][3]
Recently, phenibut (β-phenyl-GABA), a close analogue of pregabalin (β-isobutyl-GABA), has been found to similarly bind to and block α2δ-containing VDCCs, notably with an affinity exceeding that of its other actions, effectively making it a gabapentinoid.[6] Baclofen (β-(4-chlorophenyl)-GABA) has also been found to do this, but relatively weakly.[6]
See also[edit]
References[edit]
- ^ a b c Elaine Wyllie; Gregory D. Cascino; Barry E. Gidal; Howard P. Goodkin (17 February 2012). Wyllie's Treatment of Epilepsy: Principles and Practice. Lippincott Williams & Wilkins. p. 423. ISBN 978-1-4511-5348-4.
- ^ a b Honorio Benzon; James P. Rathmell; Christopher L. Wu; Dennis C. Turk; Charles E. Argoff; Robert W Hurley (11 September 2013). Practical Management of Pain. Elsevier Health Sciences. p. 1006. ISBN 978-0-323-17080-2.
- ^ a b Douglas Kirsch (10 October 2013). Sleep Medicine in Neurology. John Wiley & Sons. p. 241. ISBN 978-1-118-76417-6.
- ^ Vinik A, Rosenstock J, Sharma U, Feins K, Hsu C, Merante D, et al. Efficacy and safety of mirogabalin (DS-5565) for the treatment of diabetic peripheral neuropathic pain: a randomized, double-blind, placebo- and active comparator-controlled, adaptive proof-of-concept phase 2 study. Diabetes Care. 2014 Dec;37(12):3253-61. doi: 10.2337/dc14-1044. PMID 25231896
- ^ Alan F. Schatzberg; Charles B. Nemeroff (2009). The American Psychiatric Publishing Textbook of Psychopharmacology. American Psychiatric Pub. pp. 767–777. ISBN 978-1-58562-309-9.
- ^ a b Zvejniece, Liga; Vavers, Edijs; Svalbe, Baiba; Veinberg, Grigory; Rizhanova, Kristina; Liepins, Vilnis; Kalvinsh, Ivars; Dambrova, Maija (2015). "R-phenibut binds to the α2–δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects". Pharmacology Biochemistry and Behavior 137: 23–29. doi:10.1016/j.pbb.2015.07.014. ISSN 0091-3057.
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- (abridged; see here for a full list): α-EMTBL
- Alcohols (e.g., ethanol)
- Avermectins (e.g., ivermectin)
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- Fluoxetine
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- Lanthanum
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- Niacin
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- ROD-188
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- Topiramate
- Valerian constituents (e.g., valerenic acid)
- Volatiles/gases (e.g., chloral hydrate, chloroform, diethyl ether, paraldehyde, sevoflurane)
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- 1,3M1B
- 3M2B
- 17-Phenylandrostenol
- α5IA (LS-193,268)
- β-CCB
- β-CCE
- β-CCM
- β-CCP
- β-EMGBL
- Amiloride
- Anisatin
- β-Lactams (e.g., penicillins, cephalosporins, carbapenems)
- Basmisanil
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- Bilobalide
- CHEB
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- DHEA
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- (+)-DMBB
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- EBOB
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- L-655,708
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- Ro 19-4603
- RO4882224
- RO4938581
- Sarmazenil
- SCS
- Suritozole
- TB-21007
- TBOB
- TBPS
- TCS-1105
- Terbequinil
- TETS
- Thujone
- U-93631
- Zinc
- ZK-93426
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- Ziconotide
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- Opioids (e.g., hydrocodone, morphine, oxycodone, methadone, buprenorphine, tramadol, tapentadol)
- Sodium oxybate (GHB)
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