肟类药物抗敌敌畏对离体大鼠膈神经膈肌抑制的研究

Study on the oximes against the inhibition of DDVP on isolated rat phrenic diaphragm

目的研究ＨＩ－６、ＰＡＭ－Ｃｌ、ＰＡＭ－Ｉ和双复磷等肟类药物对抗敌敌畏抑制离体大鼠膈肌的作用机制。方法用２．５×１０－３ｍｏｌ／Ｌ敌敌畏完全抑制大鼠离体膈神经膈肌传导，然后洗掉毒剂，加药对抗：用外加５．６×１０－５ｍｏｌ／Ｌ乙酰胆碱（ＡＣｈ）的方法来检验药物是以中毒酶的重活化作用为主，还是以直接生理对抗作用为主。结果ＨＩ－６抗敌敌畏作用主要是直接生理对抗作用，ＰＡＭ－Ｃｌ、ＰＡＭ－Ｉ和双复磷抗敌敌畏的作用主要是中毒酶的重活化作用；４种药物在１×１０－３ｍｏｌ／Ｌ的浓度下，总体药效无明显差异，方差分析：Ｐ＞０．０５。结论ＨＩ－６是一种较好的抗敌敌畏所致外周呼吸肌麻痹药物；其它３种药物也有一定的直接生理对抗作用。

Objective This paper is to study the mechanism of HI 6,PAM Cl,PAM I and obidoxime against the inhibition of DDVP on isolated rat phrenic diaphragm. Methods The neuromuscular transmission in isolated rat phrenic diaphragm was inhibited completely by 2.5×10 3 mol/L DDVP,then washed out the toxicants and the neuromuscular transmission(NMT) was recoverd by incubation with the above oximes respectively.Additonal acetylcholine(ACh,5.6×10 5 mol/L ) was added to test whether there was reactivation on cholinesterase(ChE),or direct physiological antagonism. Results HI 6 mainly had direct antagonistic effect whereas obidoxime,PAM Cl and PAM I chiefly reactivated ChE.There were no significant difference of the total effects of four drugs at the concentration of 1×10 3 mol/L ( P > 0.05). Conclusion HI 6 is an effective antidote to DDVP induced phrenic paralysis,the other three drugs also have some direct physiological antagonism.