Gabazine

Gabazine

Gabazine
Systematic (IUPAC) name
2-(3-carboxypropyl)-6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-iminium bromide
Identifiers
CAS Registry Number  Y
ATC code None
PubChem CID:
ChemSpider  Y
ChEMBL  Y
Chemical data
Formula C15H18BrN3O3
Molecular mass 368.226
 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 α4βδ subunit-containing GABAA 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.  
  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.  
  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.  
  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.