title: The voltage-gated sodium ion channel inhibitory activities of a new tetrodotoxin analogue, 4,4a-anhydrotetrodotoxin, and three other analogues evaluated by colorimetric cell-based assay.
abstract: The voltage-gated sodium ion channel inhibitory activities of four tetrodotoxin analogues were evaluated for their ability to reduce the cytotoxicity of ouabain and veratridine in mouse neuroblastoma Neuro-2a cells. EC50 of the novel analogue, 4,4a-anhydrotetrodotoxin purified from pufferfish, was 750 fold larger than that of tetrodotoxin, supporting the implication of 4-OH in activity. The high activity of 11-oxotetrodotoxin was confirmed. Modification of C-6 of 11-nortetrodotoxin-6,6-diol to form an oxime derivative decreased the activity to 1/22.
authors.affiliation: Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi, 981-8555, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Saruhashi
authors.affiliation: Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi, 981-8555, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Konoki
authors.affiliation: Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi, 981-8555, Japan. Electronic address: myama@biochem.tohoku.ac.jp.
authors.forename: Mari
authors.initials: M
authors.lastname: Yotsu-Yamashita
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015640:Ion Channel Gating; D051379:Mice; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D026941:Sodium Channel Blockers; C047739:anhydrotetrodotoxin; D013779:Tetrodotoxin
keywords: 11-Oxotetrodotoxin; 4,4a-anhydrotetrodotoxin; Maleimide; Neuro-2a; Tetrodotoxin; Voltage-gated sodium ion channel