Gabazine Gabazine bromide
ATC code
2-(3-carboxypropyl)-6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-iminium bromide
CAS Number PubChem CID ChemSpider UNII ChEMBL CompTox Dashboard (EPA ) Formula C 15 H 18 Br N 3 O 3 Molar mass 368.226 g·mol−1 3D model (JSmol )
[Br-].C(=O)(O)CCCN1N=C(C=CC1=[NH2+])C1=CC=C(C=C1)OC
InChI=1S/C15H17N3O3.BrH/c1-21-12-6-4-11(5-7-12)13-8-9-14(16)18(17-13)10-2-3-15(19)20;/h4-9,16H,2-3,10H2,1H3,(H,19,20);1H
Y Key:GFZHNFOGCMEYTA-UHFFFAOYSA-N
Y
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 (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): 2170–81. doi :10.1111/j.1460-9568.2007.05462.x . PMID 17419756 . S2CID 85328190 .
^ Ueno, S; Bracamontes, J; Zorumski, C; Weiss, DS; Steinbach, JH (1997). "Bicuculline and gabazine are allosteric inhibitors of channel opening of the GABAA receptor" . The Journal of Neuroscience . 17 (2): 625–34. doi :10.1523/jneurosci.17-02-00625.1997 . PMC 6573228 . PMID 8987785 .
^ Yeung, JY; Canning, KJ; Zhu, G; Pennefather, P; MacDonald, JF; Orser, BA (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, Knudsen GM, Bräuner-Osborne H, Frølund B, Clausen RP, Chebib M, Wellendorph P (2012). "α4βδ GABA(A) receptors are high-affinity targets for γ-hydroxybutyric acid (GHB)" . Proc. Natl. Acad. Sci. U.S.A . 109 (33): 13404–9. Bibcode :2012PNAS..10913404A . doi :10.1073/pnas.1204376109 . PMC 3421209 . PMID 22753476 .
Ionotropic
GABAA
Positive modulators (abridged; see here for a full list):
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
(e.g., sulfonmethane (sulfonal) )
Topiramate
Valerian constituents (e.g., valerenic acid )
Volatiles /gases (e.g., chloral hydrate , chloroform , diethyl ether , paraldehyde , sevoflurane )
Negative modulators:
11-Ketoprogesterone
17-Phenylandrostenol
α5IA (LS-193,268)
Anabolic steroids
Amiloride
Anisatin
β-Lactams (e.g., penicillins , cephalosporins , carbapenems )
Basmisanil
Bemegride
Bicyclic phosphates (TBPS , TBPO , IPTBO )
BIDN
Bilobalide
Bupropion
Chlorophenylsilatrane
Cicutoxin
Cloflubicyne
Cyclothiazide
DHEA
DHEA-S
Dieldrin
DMCM
EBOB
FG-7142 (ZK-31906)
(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
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
PWZ-029
Radequinil
Ro 15-4513
Sarmazenil
Suritozole
TB-21007
TBPS
Terbequinil
TETS
Thujone
Zinc
ZK-93426
GABAA -ρ
Metabotropic
See also
Receptor/signaling modulators
GABAA receptor positive modulators
GABA metabolism/transport modulators
Receptor (ligands )
Transporter (blockers )
Enzyme (inhibitors )
SSR GHBDH
Enhancers: D -Glucuronic acid
HOT ADH
Cimetidine
Ethanol
Fomepizole (4-methylpyrazole)
Pyrazole
ALDH
Acetaldehyde
Cimetidine
Cyanamide
Disulfiram
Prunetin
See also
Receptor/signaling modulators
GABA receptor modulators
Glutamate receptor modulators
Glycine receptor modulators
GABA receptor antagonists GABA synthesis inhibitors Glycine receptor antagonists Glutamate receptor agonists Other