Gabapentinoid

Chemical structure of pregabalin

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][3][5]

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 extremely weakly and likely insignificantly relative to its primary action of activation of the GABAB receptor.[6]

See also

References

  1. 1 2 3 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.
  2. 1 2 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.
  3. 1 2 Douglas Kirsch (10 October 2013). Sleep Medicine in Neurology. John Wiley & Sons. p. 241. ISBN 978-1-118-76417-6.
  4. ↑ Vinik A, Rosenstock J, Sharma U, Feins K, Hsu C, Merante D; et al. (Dec 2014). "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 37 (12): 3253–61. doi:10.2337/dc14-1044. PMID 25231896.
  5. ↑ 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.
  6. 1 2 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. PMID 26234470.


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