Effect of SB-205384 on the decay of GABA-activated chloride currents in granule cells cultured from rat cerebellum.
1. 4-Amino-7-hydroxy-2-methyl-5,6,7,8,-tetrahydrobenzo[b]thieno[2,3-b]pyrid ine-3-carboxylic acid, but-2-ynyl ester (SB-205384) and other gamma-aminobutyric acid(A) (GABA(A)) 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. 2. The major effect of SB-205384 on GABA(A)-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 GABA(A) receptor modulators that have previously been shown to potentiate GABA-activated currents. 3. 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.
Meadows
H J
HJ
Neurosciences Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex.
Harries
M H
MH
Thompson
M
M
Benham
C D
CD
D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects*; D018757:GABA Modulators / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000631:Aminopyridines; D018118:Chloride Channels; D018757:GABA Modulators; D011963:Receptors, GABA-A; D013876:Thiophenes; C108120:SB 205384; D005680:gamma-Aminobutyric Acid