SKF 89976A hydrochloride

SKF 89976A hydrochloride is a potent inhibitor of GABA uptake with IC50 of 0.13, 550, 944 and 7210 μM for hGAT-1, rGAT-2, hGAT-3 and hBGT-1 respectively. GABA transporter subtype 1 (GAT-1) and GABA transporter subtype 3 (GAT-3) are the main transporters that regulate inhibitory GABAergic transmission in the mammalian brain through GABA reuptake. GAT-1 inhibitor SKF 89976A significantly prolonged the decay time, but did not affect the amplitude, of eIPSCs induced by striatal stimulation (15-20 V). Furthermore, SKF 89976A blockade also increased the amplitude and frequency of spontaneous IPSCs, but did not affect miniature IPSCs. SKF 89976A inhibits transport current competitively (Ki = 7 μM) and transmitter-gated current non-competitively (Ki = 0.03 nM). In vivo, SKF 89976A is able to pass the blood-brain barrier after systemic administration and is active.