A new glibenclamide-insensitive neuroselective hyperpolarizing agent.
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.
Hunnicutt
E J
EJ
Miles Institute for Dementia Research, West Haven, CT 06516.
Davis
J N
JN
Chisholm
J C
JC
D000818:Animals; D002478:Cells, Cultured; D005905:Glyburide / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009574:Nitro Compounds / Q000494:pharmacology*; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats
D009574:Nitro Compounds; D010671:Phenylurea Compounds; D015221:Potassium Channels; C079478:Bay Q 3111; D011188:Potassium; D005905:Glyburide