title: Na+ and high-voltage-activated Ca2+ channel blocking actions of NS-7, a novel neuroprotective agent, in NG108-15 cells.
abstract: The actions of a novel neuroprotective compound, 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride (NS-7), on voltage-gated Na+, Ca2+ and K+ channels were investigated in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, using a whole-cell voltage clamp technique. NG108-15 cells have a tetrodotoxin-sensitive Na+ channel, three types of Ca2+ channel (L, N and T) and voltage-gated K+ channels, all of which were inhibited by NS-7 in a concentration-dependent manner. However, there was a considerable difference in its potency: the IC50 values for the tetrodotoxin-sensitive Na+ channel, L-type Ca2+ channel and N-type Ca2+ channel were similar (7.8, 4.5 and 7.3 microM, respectively), lower than the IC50 value for the T-type Ca2+ channel (17.1 microM), and much lower than the IC50 value for the voltage-gated K+ channel (160.5 microM). NS-7 altered neither the shape nor the reversal potential of the current-voltage curves for Na+, L-type or N-type Ca2+ channels, although the currents were reduced at every potential tested. These results indicate that NS-7 is a Na+ and high-voltage-activated (L- and N-type) Ca2+ channel blocker, and its channel-blocking properties may contribute to its neuroprotective action.
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Suma
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Ukai
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshikuni
authors.forename: K
authors.initials: K
authors.lastname: Kimura
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D026941:Sodium Channel Blockers; D014407:Tumor Cells, Cultured
chemical_list: C106144:4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride; D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D026902:Potassium Channel Blockers; D011743:Pyrimidines; D026941:Sodium Channel Blockers