Chang C C, Su M J, Hong S J, Shieh B H, Chiou L C
J Pharm Pharmacol. 1986 Feb;38(2):153-5. doi: 10.1111/j.2042-7158.1986.tb04534.x.
Cobrotoxin was about 11-fold more potent than (+)-tubocurarine on a weight basis in blocking neuromuscular transmission in mouse isolated phrenic nerve-diaphragm preparations. Neostigmine and diaminopyridine increased the concentrations of cobrotoxin for 70% inhibition of indirect contraction by 290 and 320%, and increased those of (+)-tubocurarine by 180 and 230%, respectively. More than additive increases were obtained when neostigmine and diaminopyridine were used simultaneously. Cobrotoxin, however, was only 6-fold more toxic than (+)-tubocurarine after intraperitoneal injection in mice. The lethal dose of (+)-tubocurarine was increased by 80% when both antidotes were used together, but only by 15-20% when used alone. In contrast, the lethality of cobrotoxin was not decreased by these drugs. Unexpectedly, the time to death after treatment with cobrotoxin was shortened when mice were pretreated with these antidotes.
在小鼠离体膈神经 - 膈肌标本中,按重量计算,眼镜蛇毒素在阻断神经肌肉传递方面的效力比(+) - 筒箭毒碱强约11倍。新斯的明和二氨基吡啶使抑制间接收缩达70%时的眼镜蛇毒素浓度分别增加290%和320%,使(+) - 筒箭毒碱的浓度分别增加180%和230%。新斯的明和二氨基吡啶同时使用时,增加幅度超过相加作用。然而,在小鼠腹腔注射后,眼镜蛇毒素的毒性仅比(+) - 筒箭毒碱大6倍。两种解毒剂一起使用时,(+) - 筒箭毒碱的致死剂量增加了80%,但单独使用时仅增加15 - 20%。相比之下,这些药物并未降低眼镜蛇毒素的致死性。出乎意料的是,用这些解毒剂预处理小鼠后,注射眼镜蛇毒素后的死亡时间缩短了。