A novel Na+/Ca2+ channel blocker NS-7 inhibits evoked but not spontaneous dopamine release from rat striatum, as measured by intracerebral microdialysis.
The spontaneous dopamine release from rat striatum, measured by intracerebral microdialysis, was markedly reduced by local perfusion of tetrodotoxin (1 microM) through the dialysis probe. In addition, striatal microinjection of omega-conotoxin GVIA (10 pmol) or omega-agatoxin i.v.A (1 pmol), but not local perfusion of nimodipine, suppressed the spontaneous dopamine release. Therefore, the spontaneous dopamine release may depend on the activity of both Na+ channel as well as N-type and P/Q-type Ca2+ channels. In contrast, local perfusion of a novel Na+- and Ca2+-channel blocker NS-7 (10 microM) did not affect spontaneous dopamine release, whereas it markedly blocked KCl- and veratridine-evoked dopamine release. Therefore, NS-7 may block Na+- and Ca2+-channels only when the ion channels are highly activated.
Itoh
Y
Y
Research Laboratories, Nippon Shinyaku Co. Ltd., Kyoto, Japan.
Oka
M
M
Ukai
Y
Y
Kimura
K
K
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers; D013111:Spider Venoms / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
C106144:4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride; D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D010455:Peptides; D011743:Pyrimidines; D026941:Sodium Channel Blockers; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D013779:Tetrodotoxin; D009553:Nimodipine; D020866:omega-Conotoxin GVIA; D004298:Dopamine