A NEW GLIBENCLAMIDE-INSENSITIVE NEUROSELECTIVE HYPERPOLARIZING AGENT

We describe a novel compound, 1,2,3-trimethylpropyl)-2-nitroethene-1,1 -diamine), Bay x9227, that demonstrates dose-dependent hyperpolarizing activity of remarkable potency (EC(50) 3 picomolar) and selectivity f or CNS neurons and clonal neurotypic cells compared to smooth muscle c ells. Single cell membrane potential measurements were obtained in phy siologic buffer using the fluorescent probe, bisoxonol. Unlike K-ATP()-channel activators including its (+)-enanti-omer (Hoffman et al., 19 93, Biochem. Biophys. Res. Commun. 190(2), 551), this activity was ins ensitive to glibenclamide antagonism. These data suggest a novel pharm acologic site for effecting neuroselective hyperpolarization.