A new glibenclamide-insensitive neuroselective hyperpolarizing agent.

E J Hunnicutt; J N Davis; J C Chisholm

doi:10.1016/0014-2999(94)90325-5

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A new glibenclamide-insensitive neuroselective hyperpolarizing agent.

E J Hunnicutt·J N Davis·J C Chisholm

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Abstract

We describe a novel compound, (-)-N-(2-ethoxyphenyl)-N'-(1,2,3-trimethylpropyl)-2-nitroethene-1, 1-diamine), Bay x9227, that demonstrates dose-dependent hyperpolarizing activity of remarkable potency (EC50 3 picomolar) and selectivity for CNS neurons and clonal neurotypic cells compared to smooth muscle cells. Single cell membrane potential measurements were obtained in physiologic buffer using the fluorescent probe, bisoxonol. Unlike K+ATP-channel activators including its (+)-enantiomer (Hoffman et al., 1993, Biochem. Biophys. Res. Commun. 190(2), 551), this activity was insensitive to glibenclamide antagonism. These data suggest a novel pharmacologic site for effecting neuroselective hyperpolarization.

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Animals Cells, Cultured Glyburide Membrane Potentials Muscle, Smooth Neurons Nitro Compounds Phenylurea Compounds Potassium Potassium Channels Rats Journal Article

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E J Hunnicutt, J N Davis, J C Chisholm. 1994-08-11. A new glibenclamide-insensitive neuroselective hyperpolarizing agent.. https://doi.org/10.1016/0014-2999(94)90325-5

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