Gabapentinoids
 |
This article is a stub. As such, it may contain incomplete or wrong information. You can help by expanding it. |
Gabapentinoids, also known as α2δ ligands, are a relatively small chemical class of psychoactive substances derived from gamma-aminobutyric acid (GABA).[citation needed] Members of this class include gabapentin, F-phenibut, phenibut and pregabalin.
Gabapentinoids are commonly prescribed for epilepsy, neuropathic pain, and restless legs syndrome. Subjective effects include sedation, muscle relaxation, and anxiety suppression.
Gabapentinoids can be dangerous when mixed with other depressants such as benzodiazepines, alcohol and opioids.
Chemistry
Gabapentinoids are close structural relatives, and are all 3-substituted derivatives of GABA, the differences being the addition of a cyclohexyl group on the GABA chain in the case of gabapentin, the substitution of that cyclohexyl group for an isobutyl group in the case of pregabalin, and the substitution of that isobutyl group with a cyclic phenyl ring in the case of phenibut. Hence, they are GABA analogues, as well as γ-amino acids.[1][2]
Gabapentinoids closely resemble the α-amino acids L-leucine and L-isoleucine, and this may be of greater relevance in relation to their pharmacodynamics than their structural similarity to GABA.[3]
Pharmacology
Gabapentinoids act by inhibiting the α2δ subunit-containing voltage-dependent calcium channels (VGCCs).[4] While all gabapentinoids block the α2δ channels, they also have unique pharmacological characteristics such as enzyme inhibition.[5] The gabapentinoids are selective in their binding to the α2δ VDCC subunit.[6]
The endogenous α-amino acids L-leucine and L-isoleucine, which closely resemble the gabapentinoids in chemical structure, are apparent ligands of the α2δ VDCC subunit with similar affinity as gabapentin and pregabalin, and are present in human cerebrospinal fluid at micromolar concentrations.[3]
Pregabalin has demonstrated significantly greater potency (about 2.5-fold) than gabapentin in clinical studies.[7]
Examples
See also
External links
References
- ↑ 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.
- ↑ 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.
- ↑ 3.0 3.1 Dooley DJ, Taylor CP, Donevan S, Feltner D (2007). "Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission". Trends Pharmacol. Sci. 28 (2): 75–82. doi:10.1016/j.tips.2006.12.006. PMID 17222465.
- ↑ Patel, R., & Dickenson, A. H. (2016). Mechanisms of the gabapentinoids and α2δ‐1 calcium channel subunit in neuropathic pain. Pharmacology research & perspectives, 4(2).https://doi.org/10.1002/prp2.205
- ↑ Goldlust, A., Su, T. Z., Welty, D. F., Taylor, C. P., & Oxender, D. L. (1995). Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA. Epilepsy research, 22(1), 1-11.https://doi.org/10.1016/0920-1211(95)00028-9
- ↑ 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.
- ↑ Schifano F, D'Offizi S, Piccione M, Corazza O, Deluca P, Davey Z, Di Melchiorre G, Di Furia L, Farré M, Flesland L, Mannonen M, Majava A, Pagani S, Peltoniemi T, Siemann H, Skutle A, Torrens M, Pezzolesi C, van der Kreeft P, Scherbaum N (2011). "Is there a recreational misuse potential for pregabalin? Analysis of anecdotal online reports in comparison with related gabapentin and clonazepam data". Psychother Psychosom. 80 (2): 118–22. doi:10.1159/000321079. hdl:2299/9328. PMID 21212719. S2CID 11172830.