GABA analogue



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.

Deaminated

 * Butyric acid (butanoic acid) – histone deacetylase inhibitor and full agonist of free fatty acid receptor 2, free fatty acid receptor 3, and niacin receptor 1
 * Derivatives: butyrate (butanoate), sodium butyrate, methyl butyrate, ethyl butyrate, butyl butyrate, pentyl butyrate
 * Valeric acid (pentanoic acid) – constituent of valerian; has an unpleasant 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 GABAA 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 GABAA 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 GABAB 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, and anxiolytic; 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, GABAB receptor agonist.
 * Baclofen (β-(4-chlorophenyl)-GABA) – antispasmodic drug; potent GABAB receptor agonist, weak inhibitor of α2δ subunit-containing VGCCs
 * Tolibut (β-(4-methylphenyl)-GABA) – analgesic, tranquilizing, and neuroprotective drug
 * Phaclofen (phosphonobaclofen) – GABAB receptor antagonist
 * Saclofen (sulfonobaclofen) – GABAB receptor antagonist

Cyclized

 * 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 – GABAA receptor agonist
 * Guvacine – constituent of areca nuts; GABA reuptake inhibitor
 * Isoguvacine – GABAA receptor agonist
 * Isonipecotic acid – GABAA receptor partial agonist
 * Muscimol – constituent of Amanita muscaria mushrooms; GABAA 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 GABAA and GHB receptors
 * GAVA (γ-aminopentanoic acid) – GABA reuptake inhibitor
 * Glufimet (dimethyl 3-phenylglutamate hydrochloride) – experimental drug related to phenibut
 * Glutamic acid (glutamate) – neurotransmitter
 * Homotaurine (tramiprosate) – GABAA receptor agonist, GABAB receptor antagonist
 * Hopantenic acid (N-pantoyl-GABA) – central nervous system depressant used in Russia
 * Isovaline – peripherally selective agonist of the GABAB receptor
 * Lesogaberan (AZD-3355) – agonist of the GABAB receptor
 * N-Anisoyl-GABA – major active metabolite of the nootropic aniracetam
 * NCS-382 – antagonist of the GHB receptor
 * Piracetam and other racetams – nootropics
 * Pivagabine (N-pivaloyl-GABA) – antidepressant/anxiolytic drug; CRF inhibitor
 * Vigabatrin (y-vinyl-GABA) – anticonvulsant; GABA-T inhibitor