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COMPARATIVE STUDY
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Biological activity of 8,11-dideoxytetrodotoxin: lethality to mice and the inhibitory activity to cytotoxicity of ouabain and veratridine in mouse neuroblastoma cells, Neuro-2a.
Contribution of the C-8 hydroxyl group of tetrodotoxin to its sodium channel blocking activity has never been clearly evaluated. Isobe et al. recently synthesized 8,11-dideoxytetrodotoxin, the first 8-deoxy analog of tetrodotoxin. In this study, the biological activity of this compound was investigated to compare with that of 11-deoxytetrodotoxin. Intraperitoneal injection of 8,11-dideoxytetrodotoxin at the level of 700 microg/kg did not kill a mouse (n=2), indicating that the lethal dose of this compound was more than 70 and 10 folds larger than LD(50) of tetrodotoxin and 11-deoxytetrodotoxin, respectively. The inhibitory activity of 8,11-dideoxytetrodotoxin to cytotoxicity of ouabain and veratridine in mouse neuroblastoma cells (Neuro-2a) was also examined. The ED(50) for 8,11-dideoxytetrodotoxin was estimated to be 9.3+/-3.3 microM (n=3), approximately 2000 and 34 folds larger than those of tetrodotoxin (4.6+/-0.70 nM, n=3) and 11-deoxytetrodotoxin (270+/-74 nM, n=4), respectively. These data suggest that the C-8 hydroxyl group of tetrodotoxin is also important for its activity, as well as all the other hydroxyl groups.
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