GABRA5

Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the GABRA5 gene.[1][2]

## Contents

* 1 Function
* 2 Subunit selective ligands
* 2.1 Agonists
* 2.2 Antagonists
* 3 See also
* 4 References
* 5 Further reading
* 6 External links

## Function

GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABAA receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABAA receptor. At least 16 distinct subunits of GABAA receptors have been identified. Transcript variants utilizing three different alternative non-coding first exons have been described.[1]

## Subunit selective ligands

Recent research has produced several ligands which are moderately selective for GABAA receptors containing the α5 subunit. These have proved to be useful in investigating some of the side effects of benzodiazepine and nonbenzodiazepine drugs, particularly the effects on learning and memory such as anterograde amnesia. Inverse agonists at this subunit have nootropic effects and may be useful for the treatment of cognitive disorders such as Alzheimer's disease.

### Agonists

* QH-ii-066
* SH-053-R-CH3-2′F

### Antagonists

* α5IA
* Basmisanil (RG-1662, RO5186582): derivative of Ro4938581, negative allosteric modulator at GABAA α5, in human trials for treating cognitive deficit in Down syndrome.[3]
* L-655,708
* MRK-016
* PWZ-029: moderate inverse agonist[4]
* Pyridazines[5]
* Ro4938581[6]
* TB-21007[7][8]

## See also

* GABAA receptor

## References

1. ↑ 1.0 1.1 "Entrez Gene: GABRA5 gamma-aminobutyric acid (GABA) A receptor, alpha 5". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2558.
2. ↑ "Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit". Biochemical Society Transactions 20 (1): 18S. February 1992. doi:10.1042/bst020018s. PMID 1321750.
3. ↑ "Down syndrome and personalized medicine: changing paradigms from genotype to phenotype to treatment". Congenital Anomalies 53 (1): 1–2. March 2013. doi:10.1111/cga.12000. PMID 23480351.
4. ↑ "PWZ-029, a compound with moderate inverse agonist functional selectivity at GABA(A) receptors containing alpha5 subunits, improves passive, but not active, avoidance learning in rats". Brain Research 1208: 150–159. May 2008. doi:10.1016/j.brainres.2008.02.020. PMID 18394590.
5. ↑ "A new pyridazine series of GABAA alpha5 ligands". Journal of Medicinal Chemistry 48 (19): 6004–6011. September 2005. doi:10.1021/jm050249x. PMID 16162003.
6. ↑ "RO4938581, a novel cognitive enhancer acting at GABAA alpha5 subunit-containing receptors". Psychopharmacology 202 (1–3): 207–223. January 2009. doi:10.1007/s00213-008-1357-7. PMID 18936916.
7. ↑ "6,7-Dihydro-2-benzothiophen-4(5H)-ones: a novel class of GABA-A alpha5 receptor inverse agonists". Journal of Medicinal Chemistry 45 (6): 1176–1179. March 2002. doi:10.1021/jm010471b. PMID 11881985.
8. ↑ "Identification of a novel, selective GABA(A) alpha5 receptor inverse agonist which enhances cognition". Journal of Medicinal Chemistry 46 (11): 2227–2240. May 2003. doi:10.1021/jm020582q. PMID 12747794.

## Further reading

* "GABA(A) receptor alpha5 subunit as a candidate gene for autism and bipolar disorder: a proposed endophenotype with parent-of-origin and gain-of-function features, with or without oculocutaneous albinism". Autism 11 (2): 135–147. March 2007. doi:10.1177/1362361307075705. PMID 17353214.
* "The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder". Neuroscience Letters 381 (1–2): 108–113. 2005. doi:10.1016/j.neulet.2005.02.010. PMID 15882799.
* "Modelling extracellular domains of GABA-A receptors: subtypes 1, 2, 3, and 5". Biochemical and Biophysical Research Communications 316 (3): 636–642. April 2004. doi:10.1016/j.bbrc.2004.02.098. PMID 15033447. Bibcode: 2004BBRC..316..636C.
* "A large polymorphic repeat in the pericentromeric region of human chromosome 15q contains three partial gene duplications". Human Molecular Genetics 7 (8): 1253–1260. August 1998. doi:10.1093/hmg/7.8.1253. PMID 9668167.
* "Human gamma-aminobutyric acid-type A receptor alpha5 subunit gene (GABRA5): characterization and structural organization of the 5' flanking region". Genomics 42 (3): 378–387. June 1997. doi:10.1006/geno.1997.4770. PMID 9205108.
* "Structure and organization of GABRB3 and GABRA5". Genomics 41 (1): 63–69. April 1997. doi:10.1006/geno.1997.4639. PMID 9126483.
* "FISH ordering of reference markers and of the gene for the alpha 5 subunit of the gamma-aminobutyric acid receptor (GABRA5) within the Angelman and Prader-Willi syndrome chromosomal regions". Human Molecular Genetics 2 (2): 183–189. February 1993. doi:10.1093/hmg/2.2.183. PMID 8388764.
* "Mapping of the beta 2 subunit gene (GABRB2) to microdissected human chromosome 5q34-q35 defines a gene cluster for the most abundant GABAA receptor isoform". Genomics 23 (3): 528–533. October 1994. doi:10.1006/geno.1994.1539. PMID 7851879.
* "Dinucleotide repeat polymorphism at the GABAA receptor alpha 5 (GABRA5) locus at chromosome 15q11-q13". Human Molecular Genetics 1 (5): 348. August 1992. doi:10.1093/hmg/1.5.348. PMID 1338907.
* "Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit". Biochemical Society Transactions 20 (1): 18S. February 1992. doi:10.1042/bst020018s. PMID 1321750.

## External links

* GABRA5+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

* v
* t
* e

Ion channel, cell surface receptor: ligand-gated ion channels

Cys-loop receptors|

| 5-HT/serotonin|

* 5-HT3
* A
* B
* C
* D
* E

|

GABA|

* GABAA
* α1
* α2
* α3
* α4
* α5
* α6
* β1
* β2
* β3
* γ1
* γ2
* γ3
* δ
* ε
* π
* θ
* GABAA-ρ
* ρ1
* ρ2
* ρ3

Glycine|

* α1
* α2
* α3
* α4
* β

Nicotinic acetylcholine|

* monomers: α1
* α2
* α3
* α4
* α5
* α6
* α7
* α9
* α10
* β1
* β2
* β3
* β4
* δ
* ε

* pentamers: (α3)2(β4)3
* (α4)2(β2)3
* (α7)5
* (α1)2(β4)3 \- Ganglion type
* (α1)2β1δε - Muscle type

Zinc|

* Zinc-activated

Ionotropic glutamates|

| Ligand-gated only|

* AMPA (1
* 2
* 3
* 4)
* Kainate
* 1
* 2
* 3
* 4
* 5

|

Voltage- and ligand-gated|

* NMDA
* 1
* 2A
* 2B
* 2C
* 2D
* 3A
* 3B
* L1A
* L1B

‘Orphan’|

* GluD
* δ1
* δ2

ATP-gated channels|

| Purinergic receptors|

* P2X
* 1
* 2
* 3
* 4
* 5
* 6
* 7

|

{{Navbox | name = GABA receptor modulators | title = GABA receptor modulators | state = collapsed | bodyclass = hlist | groupstyle = text-align:center;

| group1 = Ionotropic
|  list1 = {{Navbox|subgroup
| groupstyle = text-align:center
| groupwidth = 5em

| group1 = GABAA
| list1  =

* Agonists: (+)-Catechin
* Bamaluzole
* Barbiturates (e.g., phenobarbital)
* BL-1020
* DAVA
* Dihydromuscimol
* GABA
* Gabamide
* GABOB
* Gaboxadol (THIP)
* Homotaurine (tramiprosate, 3-APS)
* Ibotenic acid
* iso-THAZ
* iso-THIP
* Isoguvacine
* Isomuscimol
* Isonipecotic acid
* Kojic amine
* Lignans (e.g., honokiol)
* Methylglyoxal
* Monastrol
* Muscimol
* Nefiracetam
* Neuroactive steroids (e.g., allopregnanolone)
* Org 20599
* PF-6372865
* Phenibut
* Picamilon
* P4S
* Progabide
* Propofol
* Quisqualamine
* SL-75102
* TACA
* TAMP
* Terpenoids (e.g., borneol)
* Thiomuscimol
* Tolgabide
* ZAPA

* Positive modulators (abridged; see here for a full list): α-EMTBL
* Alcohols (e.g., ethanol)
* Anabolic steroids
* Avermectins (e.g., ivermectin)
* Barbiturates (e.g., phenobarbital)
* Benzodiazepines (e.g., diazepam)
* Bromide compounds (e.g., potassium bromide)
* Carbamates (e.g., meprobamate)
* Carbamazepine
* Chloralose
* Chlormezanone
* Clomethiazole
* Dihydroergolines (e.g., ergoloid (dihydroergotoxine))
* Etazepine
* Etifoxine
* Fenamates (e.g., mefenamic acid)
* Flavonoids (e.g., apigenin, hispidulin)
* Fluoxetine
* Flupirtine
* Imidazoles (e.g., etomidate)
* Kava constituents (e.g., kavain)<!--PMID: 9776662-->
* Lanthanum
* Loreclezole
* Monastrol
* Neuroactive steroids (e.g., allopregnanolone, [[Chemistry:Cholecholesterol]], THDOC)
* Niacin
* Nicotinamide (niacinamide)
* Nonbenzodiazepines (e.g., β-carbolines (e.g., [[abecarnil), cyclopyrrolones (e.g., zopiclone), imidazopyridines (e.g., zolpidem), pyrazolopyrimidines (e.g., zaleplon))
* Norfluoxetine
* Petrichloral
* Phenols (e.g., propofol)
* Phenytoin
* Piperidinediones (e.g., glutethimide)
* Propanidid
* Pyrazolopyridines (e.g., etazolate)
* Quinazolinones (e.g., methaqualone)
* Retigabine (ezogabine)
* ROD-188
* Skullcap constituents (e.g., baicalin)
* Stiripentol
* Sulfonylalkanes (e.g., sulfonmethane (sulfonal))
* Topiramate
* Valerian constituents (e.g., valerenic acid)
* Volatiles/gases (e.g., chloral hydrate, chloroform, [[Chemistry:Diethyl diethyl ether, Parparaldehyde]], sevoflurane)

* Antagonists: Bicuculline
* Coriamyrtin
* Dihydrosecurinine
* Gabazine (SR-95531)
* Hydrastine
* Hyenachin (mellitoxin)
* PHP-501
* Pitrazepin
* Securinine
* Sinomenine
* SR-42641
* SR-95103
* Thiocolchicoside
* Tutin

* Negative modulators: 1,3M1B
* 3M2B
* 11-Ketoprogesterone
* 17-Phenylandrostenol
* α5IA (LS-193,268)
* β-CCB
* β-CCE
* β-CCM
* β-CCP
* β-EMGBL
* Anabolic steroids
* Amiloride
* Anisatin
* β-Lactams (e.g., penicillins, cephalosporins, carbapenems)
* Basmisanil
* Bemegride
* Bicyclic phosphates (TBPS, TBPO, IPTBO)
* BIDN
* Bilobalide
* Bupropion
* CHEB
* Chlorophenylsilatrane
* Cicutoxin
* Cloflubicyne
* Cyclothiazide
* DHEA
* DHEA-S
* Dieldrin
* (+)-DMBB
* DMCM
* DMPC
* EBOB
* Etbicyphat
* FG-7142 (ZK-31906)
* Fiproles (e.g., fipronil)
* Flavonoids (e.g., amentoflavone, oroxylin A)
* Flumazenil
* Fluoroquinolones (e.g., ciprofloxacin)
* Flurothyl
* Furosemide
* Golexanolone
* Iomazenil (123I)
* IPTBO
* Isopregnanolone (sepranolone)
* L-655,708
* Laudanosine
* Leptazol
* Lindane
* MaxiPost
* Morphine
* Morphine-3-glucuronide
* MRK-016
* Naloxone
* Naltrexone
* Nicardipine
* Nonsteroidal antiandrogens (e.g., [[apalutamide, [[Chemistry:Bicalutbicalutamide, Enzalutenzalutamide, Chemistry:Flutamide|flut]]amide]], nilutamide)
* Oenanthotoxin
* Pentylenetetrazol (pentetrazol)
* Phenylsilatrane
* Picrotoxin (i.e., picrotin, picrotoxinin and dihydropicrotoxinin)
* Pregnenolone sulfate
* Propybicyphat
* PWZ-029
* Radequinil
* Ro 15-4513
* Ro 19-4603
* RO4882224
* RO4938581
* Sarmazenil
* SCS
* Suritozole
* TB-21007
* TBOB
* TBPS
* TCS-1105
* Terbequinil
* TETS
* Thujone
* U-93631
* Zinc
* ZK-93426

| group2 = GABAA-ρ
| list2  =

* Agonists: BL-1020
* CACA
* CAMP
* Homohypotaurine
* GABA
* GABOB
* Ibotenic acid
* Isoguvacine
* Muscimol
* N4-Chloroacetylcytosine arabinoside
* Picamilon
* Progabide
* TACA
* TAMP
* Thiomuscimol
* Tolgabide

* Positive modulators: Allopregnanolone
* Alphaxolone
* ATHDOC
* Lanthanides

* Antagonists: (S)-2-MeGABA
* (S)-4-ACPBPA
* (S)-4-ACPCA
* 2-MeTACA
* 3-APMPA
* 4-ACPAM
* 4-GBA
* cis-3-ACPBPA
* CGP-36742 (SGS-742)
* DAVA
* Gabazine (SR-95531)
* Gaboxadol (THIP)
* I4AA
* Isonipecotic acid
* Loreclezole
* P4MPA
* P4S
* SKF-97541
* SR-95318
* SR-95813
* TPMPA
* trans-3-ACPBPA
* ZAPA

* Negative modulators: 5α-Dihydroprogesterone
* Bilobalide
* Loreclezole
* Picrotoxin (picrotin, picrotoxinin)
* Pregnanolone
* ROD-188
* THDOC
* Zinc

| group2 = Metabotropic

| list2 =

GABAB|

* Agonists: 1,4-Butanediol
* 4-Fluorophenibut
* Aceburic acid
* Arbaclofen
* Arbaclofen placarbil
* Baclofen
* BL-1020
* GABA
* Gabamide
* GABOB
* GBL
* GHB
* GHBAL
* GHV
* GVL
* Isovaline
* Lesogaberan
* Phenibut
* Picamilon
* Progabide
* Sodium oxybate
* SKF-97,541
* SL 75102
* Tolgabide
* Tolibut

* Positive modulators: ADX-71441
* BHF-177
* BHFF
* BSPP
* CGP-7930
* CGP-13501
* GS-39783
* rac-BHFF
* KK-92A

* Antagonists: 2-Hydroxysaclofen
* CGP-35348
* CGP-46381
* CGP-52432
* CGP-54626
* CGP-55845
* CGP-64213
* DAVA
* Homotaurine (tramiprosate, 3-APS)
* Phaclofen
* Saclofen
* SCH-50911
* SKF-97541

* Negative modulators: Compound 14

|

| below =

See also
Receptor/signaling modulators
GABAA receptor positive modulators
GABA metabolism/transport modulators

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Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:GABRA5&oldid=4253736"
*[v]: View this template
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*[e]: Edit this template
*[GABA]: γ-Aminobutyric acid
*[GABAA]: γ-Aminobutyric acid A receptor
*[GABAA-ρ]: γ-Aminobutyric acid A-rho receptor
*[GABAB]: γ-Aminobutyric acid B receptor