Chen H M, Lin C H, Wang T M
Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Toxicol Appl Pharmacol. 1996 Nov;141(1):44-8. doi: 10.1006/taap.1996.0258.
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.
本研究调查了4-氨基吡啶（4-AP）对由石房蛤毒素（STX）诱导的神经毒性的影响。在体外，在大鼠膈神经-膈肌制备物中，石房蛤毒素（1.35 nM）可抑制神经刺激诱发的抽搐张力，而4-氨基吡啶（0.1 mM）可拮抗这种抑制作用。此外，4-氨基吡啶（0.1 mM）可恢复在青蛙缝匠肌中被0.334 nM石房蛤毒素抑制甚至消除的膜动作电位发放。体内研究表明，4-氨基吡啶（0.3 mg/kg，静脉注射）可使麻醉的石房蛤毒素中毒大鼠的呼吸频率、潮气量和血压显著恢复至正常水平。此外，在石房蛤毒素正常致死剂量（30微克/千克，腹腔注射）下，4-氨基吡啶（0.75 - 6 mg/kg，腹腔注射）不仅延长了小鼠的存活时间，还降低了小鼠的死亡率（从71%降至43%）。结果表明，4-氨基吡啶可能作为石房蛤毒素中毒的解毒剂。
