| introduction | PD-85639 is a voltage-gated sodium (Na +) channel blocker (25 μM PD85,639 blocking Na + current 75% within 10 minutes and blocking> 95% within 25 minutes; Using whole-cell patch clamp of primary rat brain neurons), shows to target rat brain Nav1.2 with both high affinity and low affinity binding modes (EC50=56 nM/40% and 20 μM/60% at pH 9.0, 5 nM/28% and 3 μM/72% at pH 7.4, for 2 nM [3H]-PD85,639, for binding rat brain synaptosomes; EC50 = 17 nM/39% and 10 μM/61%, using rat brain synaptosomal membrane at pH 9.0) and fast kinetics (t1/2=1.2 at 4°C, <0.5 minutes at 25°C), compete with local anesthetics Na + channel blockers tetracaine, bupivacaine and mepivacaine, and Na + channel activator veratrine and bat toxin (K1=0.26 μM versus 5 nM [3H]-BTX for binding to rat neonatal membranes). |
