GABA analogue: Difference between revisions

Content deleted Content added

Inline

Latest revision as of 04:40, 27 January 2024

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) – 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 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, 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, 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

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 – 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
Glufimet (dimethyl 3-phenylglutamate hydrochloride) – experimental drug related to phenibut
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

References

^ 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.

[WerryAman2013-1] 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.

[1]

@@ Line 1: / Line 1: @@
 [[Image:Gamma-Aminobuttersäure - gamma-aminobutyric acid.svg|right|thumb|300px|γ-Aminobutyric acid (GABA)]]
+{{short_description|Class of drugs}}
-A '''GABA analogue''' is a compound which is an [[structural analog|analogue]] or [[chemical derivative|derivative]] of the neurotransmitter [[γ-aminobutyric acid]] (GABA).
+A '''GABA analogue''' is a compound which is an [[structural analog|analogue]] or [[chemical derivative|derivative]] of the neurotransmitter [[gamma-Aminobutyric acid]] (GABA) (the [[IUPAC]] of which is 4-aminobutanoic acid).
-Many GABA analogues are used as [[drug]]s, especially as [[anticonvulsant]]s, [[sedative]]s, and [[anxiolytic]]s
+Many GABA analogues are used as [[drug]]s, especially as [[anticonvulsant]]s, [[sedative]]s, and [[anxiolytic]]s.
 ==List of GABA analogues==
 ===Deaminated===
-* [[Butyric acid]] (butanoic acid) – [[agonist]] of [[FFAR2]], [[FFAR3]], and [[NIACR1]], and [[HDAC inhibitor]]
+* [[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]]
-* [[Isovaleric acid]] (3-methylbutanoic acid) – constituent of [[valerian]]; has anticonvulsant effects; [[positive allosteric modulator|PAM]] of the [[GABAA receptor|GABA<sub>A</sub> receptor]]
+* [[Valeric acid]] (pentanoic acid) – constituent of valerian; has an unpleasant odor and fruity flavor and esters are used as additives
-** Esters: [[validolum]] (menthyl isovalerate) – used as an anxiolytic and sedative in [[Russia]]
+** Derivatives: [[Valeric acid#Valerate salts and esters|valerate]] (pentanoate), [[methyl valerate]], [[ethyl valerate]], [[pentyl valerate]]
-* [[Valeric acid]] (pentanoic acid) – constituent of valerian; has a pleasant odor and fruity flavor and esters are used as additives in food, perfume, and cosmetics
+* [[Isovaleric acid]] (isopentanoic acid/3-methylbutanoic acid) – constituent of [[Valeriana officinalis|valerian]]; has anticonvulsant effects; [[positive allosteric modulator|PAM]] of the [[GABAA receptor|GABA<sub>A</sub> receptor]]
-** Esters: [[Methyl valerate]] (methyl pentanoate), [[ethyl valerate]] (ethyl pentanoate), [[pentyl valerate]] (pentyl pentanoate)
+** Derivatives: [[isovalerate]] (isopentanoate/3-methylbutanoate), [[menthyl isovalerate]] (validolum) – used as an anxiolytic and sedative in [[Russia]]
-* [[Valproic acid]] (2-propylpentanoic acid) – anticonvulsant and [[mood stabilizer]]; [[enzyme inhibitor|inhibitor]] of [[histone deacetylase|HDAC]], [[SSADH]], and [[GABA-T]], [[ion channel blocker|blocker]] of [[voltage-dependent sodium channel|VDSC]]s and [[GABA reuptake inhibitor|GABA reuptake]], and [[receptor antagonist|antagonist]] of [[androgen receptor|AR]] and [[progesterone receptor|PR]]
+* [[Isovaleramide]] (isopentamide/3-methylbutanamide) – constituent of [[Valeriana officinalis|valerian]]; has anxiolytic and sedative effects; [[positive allosteric modulator|PAM]] of the [[GABAA receptor|GABA<sub>A</sub> receptor]]
-** Derivatives: [[sodium valproate]], [[valproate semisodium]], [[divalproex sodium]], [[valproate pivoxil]], [[valpromide]], [[valnoctamide]]
+* [[Valproic acid]] (2-propylpentanoic acid) – anticonvulsant/[[mood stabilizer]]; [[enzyme inhibitor|inhibitor]] of [[histone deacetylase|HDAC]], [[SSADH]], and [[GABA-T]], [[ion channel blocker|blocker]] of [[voltage-dependent sodium channel|VDSC]]s and [[GABA reuptake inhibitor|GABA reuptake]], [[androgen receptor|AR]]/[[progesterone receptor|PR]] [[receptor antagonist|antagonist]]
-* [[5-Aminovaleric acid|DAVA]] (δ-aminopentanoic acid) – GABA receptor agonist
+** 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====
-* [[γ-Hydroxybutyric acid|GHB]] (γ-hydroxybutyric acid) – [[recreational drug|drug of abuse]]; agonist of [[GHB receptor]] and [[GABAB receptor|GABA<sub>B</sub> receptor]]
+* [[3-Hydroxybutanal]] – synthetic [[hypnotic]] and [[sedative]] drug
+* [[γ-Hydroxybutyric acid|GHB]] (γ-hydroxybutyric acid) – [[neurotransmitter]], [[recreational drug|drug of abuse]]; agonist of [[GHB receptor]] and [[GABAB receptor|GABA<sub>B</sub> receptor]]
-** Derivatives: [[Sodium oxybate]] (sodium γ-hydroxybutanoate) – used to treat [[narcolepsy]], same [[mechanism of action]] as GHB
+** Derivatives: [[sodium oxybate]] (sodium γ-hydroxybutanoate) – used to treat [[narcolepsy]]; same [[mechanism of action]] as GHB
-* [[γ-Butyrolactone|GBL]] (γ-hydroxybutyric acid lactone) – [[prodrug]] to GHB
+* [[Aceburic acid]] (γ-hydroxybutyric acid acetate) – synthetic [[prodrug]] to GHB
+* [[γ-Butyrolactone|GBL]] (γ-hydroxybutyric acid lactone) – [[metabolic intermediate]] and prodrug to GHB
-* [[3-Hydroxybutanal]] – [[hypnotic]] and [[sedative]] drug
-* [[GHBAL]] (γ-hydroxybutyraldehyde or γ-hydroxybutanal) – [[metabolic intermediate]] and prodrug to GHB
+* [[GHBAL]] (γ-hydroxybutyraldehyde or γ-hydroxybutanal) – metabolic intermediate and prodrug to GHB
-* [[UMB68]] (γ-Hydroxy-γ-methylpentanoic acid) – GHB receptor agonist
+* [[γ-Hydroxyvaleric acid|GHV]] (γ-hydroxyvaleric acid) – [[designer drug]]; analogue of GHB with similar effects
+* [[γ-Valerolactone|GVL]] (γ-valerolactone) – designer drug; prodrug to GHV
+* [[trans-4-Hydroxycrotonic acid|T-HCA/GHC]] (γ-hydroxycrotonic acid) – neurotransmitter; GHB receptor agonist
+* [[γ-Crotonolactone|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]]; inhibitor of [[Voltage-dependent calcium channel#α2δ Subunit|α<sub>2</sub>δ subunit]]-containing [[voltage-gated calcium channel|VGCC]]s
+* [[Pregabalin]] (β-isobutyl-GABA) – [[analgesic]], [[anticonvulsant]], and [[anxiolytic]]; potent inhibitor of [[Voltage-dependent calcium channel#α2δ Subunit|α<sub>2</sub>δ subunit]]-containing [[voltage-gated calcium channel|VGCC]]s.
 * [[Phenibut]] (β-phenyl-GABA) – sedative and anxiolytic from Russia; inhibitor of [[Voltage-dependent calcium channel#α2δ Subunit|α<sub>2</sub>δ subunit]]-containing [[voltage-gated calcium channel|VGCC]]s and, to a lesser extent, GABA<sub>B</sub> receptor agonist.
 * [[Baclofen]] (β-(4-chlorophenyl)-GABA) – [[antispasmodic]] drug; potent GABA<sub>B</sub> receptor agonist, weak inhibitor of α<sub>2</sub>δ subunit-containing VGCCs
+* [[Tolibut]] (β-(4-methylphenyl)-GABA) – analgesic, [[tranquilizer|tranquilizing]], and [[neuroprotective]] drug
 * [[Phaclofen]] (phosphonobaclofen) – GABA<sub>B</sub> receptor antagonist
 * [[Saclofen]] (sulfonobaclofen) – GABA<sub>B</sub> receptor antagonist
-===Aromatized===
+===Cyclized===
 * [[Arecaidine]] – constituent of [[areca nuts]]; GABA reuptake inhibitor
 * [[Gabaculine]] – [[neurotoxin]]; GABA-T inhibitor and [[GABA reuptake inhibitor]]
@@ Line 45: / Line 57: @@
 ===GABA prodrugs===
 * [[Glutamine|<small>L</small>-Glutamine]] – endogenous [[precursor (biochemistry)|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
@@ Line 50: / Line 63: @@
 ===Others/miscellaneous===
+* [[1,4-Butanediol]] – metabolic intermediate and prodrug to GHB
 * [[3-Methyl-GABA]] – GABA-T activator
 * [[alpha-Aminobutyric acid|AABA/homoalanine]] (α-aminobutyric acid) – used by [[nonribosomal peptide]] [[synthetase]]s
 * [[beta-Aminobutyric acid|BABA]] (β-aminobutyric acid) – known for its ability to induce [[plant disease resistance]]
+* [[5-Aminovaleric acid|DAVA]] (δ-aminopentanoic acid) – GABA receptor agonist
 * [[Gabamide]] (γ-aminobutanamide) – GABA receptor agonist
 * [[Gabazine]] (SR-95531) – antagonist of the GABA<sub>A</sub> and GHB receptors
 * [[4-Aminovaleric acid|GAVA]] (γ-aminopentanoic acid) – GABA reuptake inhibitor
+* [[Glufimet]] (dimethyl 3-phenylglutamate hydrochloride) – experimental drug related to phenibut
-* [[Glutamic acid]] (glutamate) – major neurotransmitter
+* [[Glutamic acid]] (glutamate) – neurotransmitter
 * [[Homotaurine]] (tramiprosate) – GABA<sub>A</sub> receptor agonist, GABA<sub>B</sub> receptor antagonist
 * [[Hopantenic acid]] (N-pantoyl-GABA) – [[depressant|central nervous system depressant]] used in Russia
+* [[Isovaline]] – peripherally selective agonist of the GABA<sub>B</sub> receptor
 * [[Lesogaberan]] (AZD-3355) – agonist of the GABA<sub>B</sub> receptor
+* [[N-Anisoyl-GABA]] – major active metabolite of the nootropic [[aniracetam]]
 * [[NCS-382]] – antagonist of the GHB receptor
+* [[Piracetam]] and other [[racetam]]s<ref name="WerryAman2013">{{cite book|author1=John Scott Werry|author2=Michael G. Aman|title=Practitioner's Guide to Psychoactive Drugs for Children and Adolescents|url=https://books.google.com/books?id=k_2fBwAAQBAJ&pg=PA415|date=29 June 2013|publisher=Springer Science & Business Media|isbn=978-1-4899-0086-9|pages=415–}}</ref> – nootropics
 * [[Pivagabine]] (N-pivaloyl-GABA) – [[antidepressant]]/anxiolytic drug; [[corticotropin-releasing factor|CRF]] inhibitor
 * [[Vigabatrin]] (y-vinyl-GABA) – anticonvulsant; GABA-T inhibitor
@@ Line 78: / Line 97: @@
 ==References==
-{{Unreferenced|date=October 2015}}
+{{Refimprove|date=January 2017}}
-{{Reflist|2}}
+{{reflist|30em}}
 {{GABAergics}}
@@ Line 86: / Line 104: @@
 {{Channel blockers}}
-[[Category:GABA analogues]]
+[[Category:GABA analogues| ]]
 [[Category:GABA receptor agonists]]
-{{biochemistry-stub}}