SB 205384 slows the decay of GABA-activated chloride currents in granule cells cultured from rat cerebellum

Meadows, H.J., Harries, M., Thompson, M. and Benham, C.D. (1997) SB 205384 slows the decay of GABA-activated chloride currents in granule cells cultured from rat cerebellum. British Journal of Pharmacology (7). pp. 1334-1338. ISSN 0007-1188
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4-Amino-7-hydroxy-2-methyl-5,6,7,8,-tetrahydrobenzo[b]thieno[2,3-b]pyridine-3-carboxylic acid, but-2-ynyl ester (SB-205384) and other γ-aminobutyric acidA (GABAA) receptor modulators were tested for their effects on GABA-activated chloride currents in rat cerebellar granule cells by use of the whole-cell patch clamp technique. The major effect of SB-205384 on GABAA-activated current was an increase in the half-life of decay of the response once the agonist had been removed. This is in contrast to many GABAA receptor modulators that have previously been shown to potentiate GABA-activated currents. This profile could be explained if SB-205384 stabilizes the channel in open and desensitized states so that channel closing is dramatically slowed. Such a modulatory profile may produce a novel behavioural profile in vivo.

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