EFFECT OF SB-205384 ON THE DECAY OF GABA-ACTIVATED CHLORIDE CURRENTS IN GRANULE CELLS CULTURED FROM RAT CEREBELLUM

1 trahydrobenzo[b]thieno[2,3-b]pyridine-3-carboxylic acid, but-2-ynyl ester (SE-205384) and other gamma-aminobutyric acid(A) (GABA(A)) recep tor modulators were tested for their effects on GABA-activated chlorid e currents in rat cerebellar granule cells by use of the whole-cell pa tch clamp technique. 2 The major effect of SE-205384 on GABA(A)-activa ted 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 GABA(A) receptor modulators that have previously been shown to potentiate GAB A-activated currents. 3 This profile could be explained if SE-205384 s tabilizes 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.