Effects of 4-aminopyridine on saxitoxin intoxication

Effects of 4-aminopyridine (4-AP) on neurotoxicity induced by saxitoxin (STX) are investigated in this study. In vitro, twitch tension evoked by nerve stimulation was depressed by STX (1.35 nM) in rat phrenic nerve-diaphragm preparations, and this inhibition was antagonized by 4-AP (0.1 mM). In addition, 4-AP (0.1 mM) restored the firing of membrane action potentials that were suppressed or even abolished by 0.334 nM STX in frog sartorius muscles. In vivo studies showed that 4-AP (0.3 mg/kg, iv) significantly reversed the respiratory rate, tidal volume, and blood pressure to normal values in anesthetized STX-toxicosis rats. Furthermore, 4-AP (0.75-6 mg/kg, ip) not only prolonged the survival time but also decreased the mortality of mice (71-43%) at a normally lethal dose (30 micrograms/kg, ip) of STX. The results suggest that 4-AP may be useful as an antidote for STX intoxication.