positive GABAA receptor modulator
SB-205384 is a selective and positive GABAA receptor modulator with EC50 values of 280, 695 and 730 nM on α6, α3 and α5-subunit-containing receptors, respectively [1].
g-Aminobutyric acid (GABA) acting on the GABAA receptor can inhibit synaptic transmission in the mammalian central nervous system [1]. Ligands that modulate the function of g-aminobutyric acid A (GABAA) receptor gated chloride channels have hypnotic, anaesthetic, anxiolytic, anticonvulsant and sedative actions [2].
SB-205384 can slow the decay rate on GABAA currents in oocytes expressing human GABAA subunits, which is also seen on native GABA-activated currents in rat neurons [3]. The isoforms containing the a3, a5, and a6 subunits show significantly greater enhancement of the current by SB-205384 and the receptors with the a6-subunit had the greatest sensitivity to SB-205384 [1]. In rat cerebellum granule cells, SB-205384 dramatically pro-longed the half-life for decay of the GABA response in a concentration-dependent manner. The half-life of decay was increased about 10 fold compared with control responses at the highest concentration of SB-205384 used. Also, SB-205384 did not increase the maximum current evoked by 100 mM GABA but the half-life decay was dramatically increased, as saw at the lower dose of 1 mM GABA [2].
参考文献:
[1]. Heidelberg LS, Warren JW, Fisher JL. SB-205384 is a positive allosteric modulator of recombinant GABAA receptors containing rat α3, α5, or α6 subunit subtypes coexpressed with β3 and γ2 Subunits. J Pharmacol Exp Ther, 2013, 347(1): 235-241.
[2]. Meadows HJ, Harries MH, Thompson M, et al. Effect of SB-205384 on the decay of GABA-activated chloride currents in granule cells cultured from rat cerebellum. Br J Pharmacol, 1997, 121(7): 1334-1338.
[3]. Meadows HJ, Kumar CS, Pritchett DB, et al. SB-205384: a GABAA receptor modulator with novel mechanism of action that shows subunit selectivity. Br J Pharmacol, 1998, 123(6): 1253-1259.
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