Gabexate

Gabexate

Systematic (IUPAC) name
2-(3-carboxypropyl)-6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-iminium bromide
Identifiers
CAS Number	104104-50-9
ATC code	none
PubChem	CID 107895
ChemSpider	4925141
ChEMBL	CHEMBL303580
Chemical data
Formula	C15H18BrN3O3
Molar mass	368.226
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
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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

1. 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.
2. 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 : the official journal of the Society for Neuroscience 17 (2): 625–34. PMID 8987785.
3. 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.
4. 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. doi:10.1073/pnas.1204376109. PMC 3421209. PMID 22753476.