Novel Modulator of Na(v)1.1 and Na(v)1.2 Na+ Channels in Rat Neuronal Cells

by Mao, Hua; Fieber, Lynne A.; Gawley, Robert E.

A novel modulator of sodium ion currents was synthesized in 6 steps from a protected dihydroxypyrrolidine nitrone, via 1,3-dipolar cycloaddition reaction with acrylamide. Sodium ion currents in 850 cells were evaluated in comparison to saxitoxin and tetrodotoxin and revealed an IC50 of 15.7 mu M. The new compound shows no evidence of binding to the C-lobe of the saxitoxin-binding protein saxiphilin.

Journal
ACS Medicinal Chemistry Letters
Volume
1
Issue
3
Year
2010
Start Page
135
ISBN/ISSN
1948-5875
PMID
20607120
DOI
10.1021/ml100035t