From Wikipedia, the free encyclopedia
Chemical compound
Gabazine (SR-95531 ) is a
drug that acts as an
antagonist at
GABAA
receptors . It is used in scientific research and has no role in medicine, as it would be expected to produce
convulsions if used in humans.
[1]
Gabazine binds to the GABA recognition site of the receptor-channel complex and acts as an
allosteric inhibitor of channel opening.
[2] The net effect is to reduce GABA-mediated
synaptic inhibition by inhibiting
chloride flux across the cell membrane, and thus inhibiting neuronal hyperpolarization. While phasic (synaptic) inhibition is gabazine-sensitive, tonic (extrasynaptic) inhibition is relatively gabazine-insensitive.
[3]
Gabazine has been found to bind to and antagonize α4 βδ
subunit -containing GABAA receptors, which may represent the
GHB receptor .
[4]
References
^ Behrens CJ, van den Boom LP, Heinemann U (April 2007). "Effects of the GABA(A) receptor antagonists bicuculline and gabazine on stimulus-induced sharp wave-ripple complexes in adult rat hippocampus in vitro". The European Journal of Neuroscience . 25 (7): 2170–2181.
doi :
10.1111/j.1460-9568.2007.05462.x .
PMID
17419756 .
S2CID
85328190 .
^ Ueno S, Bracamontes J, Zorumski C, Weiss DS, Steinbach JH (January 1997).
"Bicuculline and gabazine are allosteric inhibitors of channel opening of the GABAA receptor" . The Journal of Neuroscience . 17 (2): 625–634.
doi :
10.1523/jneurosci.17-02-00625.1997 .
PMC
6573228 .
PMID
8987785 .
^ Yeung JY, Canning KJ, Zhu G, Pennefather P, MacDonald JF, Orser BA (January 2003). "Tonically activated GABAA receptors in hippocampal neurons are high-affinity, low-conductance sensors for extracellular GABA". Molecular Pharmacology . 63 (1): 2–8.
doi :
10.1124/mol.63.1.2 .
PMID
12488530 .
S2CID
6827514 .
^ Absalom N, Eghorn LF, Villumsen IS, Karim N, Bay T, Olsen JV, et al. (August 2012).
"α4βδ GABA(A) receptors are high-affinity targets for γ-hydroxybutyric acid (GHB)" . Proceedings of the National Academy of Sciences of the United States of America . 109 (33): 13404–13409.
Bibcode :
2012PNAS..10913404A .
doi :
10.1073/pnas.1204376109 .
PMC
3421209 .
PMID
22753476 .
Ionotropic
GABAA Tooltip γ-Aminobutyric acid A receptor
Positive modulators (abridged; see
here for a full list):
α-EMTBL
Alcohols (e.g.,
drinking alcohol ,
2M2B )
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 )
Lanthanum
Loreclezole
Monastrol
Neuroactive steroids (e.g.,
allopregnanolone ,
cholesterol ,
THDOC )
Niacin
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 ,
diethyl ether ,
paraldehyde ,
sevoflurane )
Negative modulators:
1,3M1B
3M2B
11-Ketoprogesterone
17-Phenylandrostenol
α3IA
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 (123 I)
IPTBO
Isopregnanolone (sepranolone)
L-655,708
Laudanosine
Lindane
MaxiPost
Morphine
Morphine-3-glucuronide
MRK-016
Naloxone
Naltrexone
Nicardipine
Nonsteroidal antiandrogens (e.g.,
apalutamide ,
bicalutamide ,
enzalutamide ,
flutamide ,
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
GABAA -ρ Tooltip γ-Aminobutyric acid A-rho receptor
Metabotropic
GABAB Tooltip γ-Aminobutyric acid B receptor
Receptor (
ligands )
GHBR Tooltip GHB receptor
GABAB Tooltip γ-Aminobutyric acid B receptor
Transporter (
blockers )
MCTs Tooltip Monocarboxylate transporters
SMCTs Tooltip Sodium-coupled monocarboxylate transporters
VIATT Tooltip Vesicular inhibitory amino acid transporter
Enzyme (
inhibitors )
SSR Tooltip Succinic semialdehyde reductase
GHBDH Tooltip 4-Hydroxybutyrate dehydrogenase
HOT Tooltip Hydroxyacid-oxoacid transhydrogenase
ADH Tooltip Alcohol dehydrogenase
ALDH Tooltip Aldehyde dehydrogenase