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.
Chen
H M
HM
Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Lin
C H
CH
Wang
T M
TM
D015761:4-Aminopyridine / Q000627:therapeutic use*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000187:drug effects; D010791:Phrenic Nerve / Q000187:drug effects; D011898:Ranidae; D051381:Rats; D017207:Rats, Sprague-Dawley; D012530:Saxitoxin / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D012530:Saxitoxin; D015761:4-Aminopyridine