氯甲左箭毒的受体动力学研究

本文研究了氯甲左箭毒(DMC)对N₂受体的拮抗作用,并以氯化筒箭毒碱(d-TC)为对照。在DMC作用下,ACh对蟾蜍腹直肌的累积剂量—效应%曲线平行右移,测得其pA₂=5.472,K_B=0.363±0.011(±SE),而d-TC则分别为5.635和0.258±0.010。以log(x-1)对DMC对M的负对数(-logB])作图,其回归线斜率=-0.96,同竞争性拮抗剂的理论斜率-1十分接近。此外,不管DMC的浓度如何,所计算得的K_B值基本不变。上述结果证明,DMC对N₂受体的拮抗性质确为竞争性拮抗,其对N₂受体的亲和力约为d-TC的70%。

STUDIES ON THE DRUG-RECEPTOR KINETICS OF DIMETHYLCURINE METHYLCHLORIDE

The drug-receptor interactions of dimethylcurine methylchloride (DMC) with toad rectus abdominis N₂-receptor were studied and compared with that of dtubocurarine chloride (d-TC). The antagonism of DMC to the ACh induced muscle contractions was completely overcome by increasing the concentration of ACh and the dose-cumulative-effect curves were parallel. The pA2 values of DMC and d-TC were 5.472 and 5.635 respectively. The K_B 's of DMC and d-TC were 0.363±0.011 (±SE) and 0.258±0.010 respectively. When the dose ratios log (X-1) were plotted versus negative log molar values of DMC (Schild plot), the regression slope was -0.96, very close to the theoretical value -1.0 of competitive antagonist. The calculated K_B's of different concentrations of DMC were approximately the same. These results strongly suggest that the DMC is a competitive antagonist and its affinity is about 70% that of d-TC on toad rectus abdominis.