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目的探讨苯环喹溴铵对毒蕈碱样乙酰胆碱受体(M受体)亚型的选择性。方法以表达单一M受体亚型的CHO细胞株进行细胞与[3H]-QNB的饱和实验,并进行竞争抑制药和[3H]-QNB与M受体亚型的竞争结合实验,计算Kd值和Ki值。通过离体膀胱肌条实验评价苯环喹溴铵干预乙酰胆碱对离体膀胱肌条的收缩作用,计算pA2值。观察苯环喹溴铵对麻醉犬心率、心电图的影响及其对小鼠气管分泌功能的影响。结果苯环喹溴铵对3种细胞的抑制强度为CHOM3>CHOM1>CHOM2,对CHOM3和CHOM1的抑制能力相似,明显高于对CHOM2的抑制能力(P<0.01)。苯环喹溴铵可拮抗乙酰胆碱对离体膀胱肌条的收缩作用,使量效曲线平行右移,PA2值为7.09±s0.06。与溶媒组相比,苯环喹溴铵经鼻给药后对麻醉犬的心率和心电图无明显影响(P>0.05)。苯环喹溴铵大剂量组给药后1h、2h和中剂量组给药后2h能明显减少小鼠气管分泌物的分泌(P<0.01)。结论苯环喹溴铵是一种可选择性作用于M1和M3受体亚型的拮抗药。
Objective To investigate the selectivity of phenylcyclohexaammonium for the muscarinic acetylcholine receptor (M receptor) subtype. Methods Saturation experiments of cells with [3H] -QNB were performed in CHO cell lines expressing a single M receptor subtypes. Competition-suppressing drugs and competitive binding experiments of [3H] -QNB and M receptor subtypes were performed to calculate Kd values And Ki values. The in vitro bladder stria test was used to evaluate the contractile effect of phenylcyclohexabromide on isolated bladder myoblasts, and the pA2 value was calculated. To observe the effect of phenylcyclohexaquinone on heart rate and electrocardiogram in anesthetized dogs and its effect on tracheal secretion in mice. Results The inhibitory potency of phenylcyclohexaammonium bromide against three kinds of cells was CHOM3> CHOM1> CHOM2, which showed similar inhibitory activity to CHOM3 and CHOM1, but significantly higher than that of CHOM2 (P <0.01). Benzocyclopurine can antagonize the contractile effect of acetylcholine on isolated bladder muscle strips, so that the dose-effect curve parallel shift right, PA2 value was 7.09 ± s0.06. Compared with vehicle group, benzodiazepine had no significant effect on the heart rate and electrocardiogram of anesthetized dogs after nasal administration (P> 0.05). The levels of tracheal secretions were significantly decreased at 1 h, 2 h and 2 h after administration of BenQ in the high dose group (P <0.01). Conclusions Benzyquine bromide is a selective antagonist of M1 and M3 receptor subtypes.