Gabazine

Gabazine
	Gabazine bromide
Clinical data
ATC code	none;
Identifiers
	IUPAC name 2-(3-carboxypropyl)-6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-iminium bromide;
CAS Number	104104-50-9 ;
PubChem CID	107895;
ChemSpider	4925141 ;
UNII	99460MG420;
ChEMBL	ChEMBL303580 ;
CompTox Dashboard (EPA)	DTXSID40908798 ;
Chemical and physical data
Formula	C15H18BrN3O3
Molar mass	368.231 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES [Br-].C(=O)(O)CCCN1N=C(C=CC1=[NH2+])C1=CC=C(C=C1)OC;
	InChI 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 ; Key:GFZHNFOGCMEYTA-UHFFFAOYSA-N ;
	(verify)

Gabazine (SR-95531) is a drug that acts as an antagonist at GABA_A 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 α₄βδ subunit-containing GABA_A 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.

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[1] 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.

[2] 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.

[3] 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.

[pmid22753476-4] 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.

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v t e Convulsants
GABA receptor antagonists	Bicuculline Bicyclic phosphates (TBPS, TBPO, IPTBO) BIDN Chlorophenylsilatrane Cicutoxin Cloflubicyne Coriamyrtin Dihydropicrotoxinin DMCM EBOB Endosulfan FG-7142 Fipronil Flurothyl Gabazine Oenanthotoxin Pentylenetetrazol Phenylsilatrane Picrotoxin p-CN-TBOB p-NCS-TBOB RDX TBOB Tetramethylenedisulfotetramine Thujone Trimethylolpropane phosphite Tutin
GABA synthesis inhibitors	3-Mercaptopropionic acid 4-Deoxypyridoxine Allylglycine Crimidine Decaborane Ginkgotoxin Isoniazid Pentaborane Thiocarbohydrazide Toxopyrimidine
Glycine receptor antagonists	Coriamyrtin Dendrobine Picrotoxin Strychnine Tutin
Glutamate receptor agonists	AMPA Domoic acid Kainic acid NMDA Quisqualic acid Tetrazolylglycine
Convulsant barbiturates	CHEB Diberal (DMBB) McN-481
Other	2,2,3,3-Tetrafluoropropyl trifluoromethyl ether Bromocamphor Camphor FAZ-4 Fluoroethyl fluoroacetate MC-2973 Methionine sulfoximine Methyl fluoroacetate Nitrocyclohexane Thebaine