GABA analogue

γ-Aminobutyric acid (GABA)

A GABA analogue is a compound which is an analogue or derivative of the neurotransmitter gamma-Aminobutyric acid (GABA) (the IUPAC of which is 4-aminobutanoic acid).

Many GABA analogues are used as drugs, especially as anticonvulsants, sedatives, and anxiolytics

List of GABA analogues

Deaminated

• Butyric acid (butanoic acid) – agonist of Free fatty acid receptor 2, Free fatty acid receptor 3, and Niacin receptor 1, and HDAC inhibitor
  • Derivatives: butyrate (butanoate), sodium butyrate, methyl butyrate, ethyl butyrate, butyl butyrate, pentyl butyrate
• Valeric acid (pentanoic acid) – constituent of valerian; has a pleasant odor and fruity flavor and esters are used as additives
  • Derivatives: valerate (pentanoate), methyl valerate, ethyl valerate, pentyl valerate
• Isovaleric acid (isopentanoic acid/3-methylbutanoic acid) – constituent of valerian; has anticonvulsant effects; PAM of the GABA_A receptor
  • Derivatives: isovalerate (isopentanoate/3-methylbutanoate), menthyl isovalerate (validolum) – used as an anxiolytic and sedative in Russia
• Isovaleramide (isopentamide/3-methylbutanamide) – constituent of valerian; has anxiolytic and sedative effects; PAM of the GABA_A receptor
• Valproic acid (2-propylpentanoic acid) – anticonvulsant/mood stabilizer; inhibitor of HDAC, SSADH, and GABA-T, blocker of VDSCs and GABA reuptake, AR/PR antagonist
  • Derivatives: sodium valproate, valproate semisodium, divalproex sodium, valproate pivoxil
• Valpromide (2-propylpentanamide) – anticonvulsant; same mechanism of action as valproic acid, plus inhibitor of epoxide hydrolase
• Valnoctamide (2-ethyl-3-methylpentanamide) – anticonvulsant; similar mechanism of action to valproic acid; structural isomer of valpromide

3- or 4-Hydroxylated

• 3-Hydroxybutanal – synthetic hypnotic and sedative drug
• GHB (γ-hydroxybutyric acid) – neurotransmitter, drug of abuse; agonist of GHB receptor and GABA_B receptor
  • Derivatives: sodium oxybate (sodium γ-hydroxybutanoate) – used to treat narcolepsy; same mechanism of action as GHB
• Aceburic acid (γ-hydroxybutyric acid acetate) – synthetic prodrug to GHB
• GBL (γ-hydroxybutyric acid lactone) – metabolic intermediate and prodrug to GHB
• GHBAL (γ-hydroxybutyraldehyde or γ-hydroxybutanal) – metabolic intermediate and prodrug to GHB
• GHV (γ-hydroxyvaleric acid) – designer drug; analogue of GHB with similar effects
• GVL (γ-valerolactone) – designer drug; prodrug to GHV
• T-HCA/GHC (γ-hydroxycrotonic acid) – neurotransmitter; GHB receptor agonist
• GCL (γ-crotonolactone) – prodrug to T-HCA/GHC
• HOCPCA (3-hydroxycyclopent-1-enecarboxylic acid) – synthetic GHB receptor agonist
• UMB68 (γ-hydroxy-γ-methylpentanoic acid) – synthetic GHB receptor agonist

β-Substituted

• GABOB (β-hydroxy-GABA) – anticonvulsant; GABA receptor agonist
• Pregabalin (β-isobutyl-GABA) – analgesic, anticonvulsant, anxiolytic, and drug of abuse; potent inhibitor of α₂δ subunit-containing VGCCs.
• Phenibut (β-phenyl-GABA) – sedative and anxiolytic from Russia; inhibitor of α₂δ subunit-containing VGCCs and, to a lesser extent, GABA_B receptor agonist.
• Baclofen (β-(4-chlorophenyl)-GABA) – antispasmodic drug; potent GABA_B receptor agonist, weak inhibitor of α₂δ subunit-containing VGCCs
• Tolibut (β-(4-methylphenyl)-GABA) – analgesic, tranquilizing, and neuroprotective drug
• Phaclofen (phosphonobaclofen) – GABA_B receptor antagonist
• Saclofen (sulfonobaclofen) – GABA_B receptor antagonist

Aromatized

• Arecaidine – constituent of areca nuts; GABA reuptake inhibitor
• Gabaculine – neurotoxin; GABA-T inhibitor and GABA reuptake inhibitor
• Gabapentin – anticonvulsant; inhibitor of α₂δ subunit-containing VGCCs
  • Gabapentin enacarbil – used for the treatment of restless legs syndrome and postherpetic neuralgia; same mechanism of action as gabapentin
• Gaboxadol – GABA_A receptor agonist
• Guvacine – constituent of areca nuts; GABA reuptake inhibitor
• Isoguvacine – GABA_A receptor agonist
• Isonipecotic acid – GABA_A receptor partial agonist
• Muscimol – constituent of Amanita muscaria mushrooms; GABA_A receptor agonist
• Nipecotic acid – used in scientific research; GABA reuptake inhibitor

GABA prodrugs

• L-Glutamine – endogenous precursor of GABA and glutamate
• N-Isonicotinoyl-GABA – structural isomer of picamilon
• Picamilon (N-nicotinoyl-GABA) – dietary supplement and prescription drug in Russia
• Progabide (complex structure) – anticonvulsant
• Tolgabide (complex structure) – anticonvulsant

Others/miscellaneous

• 1,4-Butanediol – metabolic intermediate and prodrug to GHB
• 3-Methyl-GABA – GABA-T activator
• AABA/homoalanine (α-aminobutyric acid) – used by nonribosomal peptide synthetases
• BABA (β-aminobutyric acid) – known for its ability to induce plant disease resistance
• DAVA (δ-aminopentanoic acid) – GABA receptor agonist
• Gabamide (γ-aminobutanamide) – GABA receptor agonist
• Gabazine (SR-95531) – antagonist of the GABA_A and GHB receptors
• GAVA (γ-aminopentanoic acid) – GABA reuptake inhibitor
• Glutamic acid (glutamate) – neurotransmitter
• Homotaurine (tramiprosate) – GABA_A receptor agonist, GABA_B receptor antagonist
• Hopantenic acid (N-pantoyl-GABA) – central nervous system depressant used in Russia
• Isovaline – peripherally selective agonist of the GABA_B receptor
• Lesogaberan (AZD-3355) – agonist of the GABA_B receptor
• N-Anisoyl-GABA – major active metabolite of the nootropic aniracetam
• NCS-382 – antagonist of the GHB receptor
• Piracetam and other racetams^[1] – nootropics
• Pivagabine (N-pivaloyl-GABA) – antidepressant/anxiolytic drug; CRF inhibitor
• Vigabatrin (y-vinyl-GABA) – anticonvulsant; GABA-T inhibitor

See also

• Bamaluzole
• Bicuculline
• Deramciclane
• Ethanol
• Fengabine
• Gabapentinoid
• Loreclezole
• Propofol
• Retigabine/ezogabine
• Tiagabine
• Valerenic acid

References

1. John Scott Werry; Michael G. Aman (29 June 2013). Practitioner’s Guide to Psychoactive Drugs for Children and Adolescents. Springer Science & Business Media. pp. 415–. ISBN 978-1-4899-0086-9.