Actions of nortetrodotoxin on frog muscle and squid axon

Nortetrodotoxin, prepared by oxidation of the C6 end of tetrodotoxin, probably exists in solution as an equilibrium mixture of a hemilactal and a lactone form of a hydrated ketone of C6. On both frog muscle fibers under constant-current conditions and squid giant axon under voltage-clamped conditions, nortetrodotoxin selectively blocks the sodium channel. On frog muscle fibers, the solution of nortetrodotoxin used, which was several months old, was 1/13 as active as tetrodotoxin. On the squid giant axon, a freshly prepared solution of nortetrodotoxin was about 1/4 as active. These observations indicate that nortetrodotoxin possesses a substantial degree of biological activity. The suitability of nortetrodotoxin as an intermediate for synthesizing derivatives of tetrodotoxin is discussed.