Gordon R K, Chiang P K
J Pharmacol Exp Ther. 1986 Jan;236(1):85-9.
The antimuscarinic activity of hycanthone and five antischistosomal analogs was determined in three biological assays of cholinergic systems. A linear relationship was established between the LD50 values of hycanthone analogs in mice and 1) the Ki values obtained from the inhibition of [3H]quinuclidinyl benzilate binding to the muscarinic receptors of N4TG1 neuroblastoma cells; 2) the I50 values obtained from the inhibition of alpha-amylase secretion induced by carbachol in pancreatic acini cells; and 3) the KB values obtained from the inhibition of guinea-pig ileum contraction induced by acetylcholine. The linear relationship established between antimuscarinic potency and toxicity in mice suggests that a possible relationship exists between the toxicity of the hycanthone analogs and their antimuscarinic activities. On the other hand, no correlation was established between antischistosomal efficacy and antimuscarinic potency. The Ki and I50 values ranged from 10(-7) to 10(-5) M for the inhibition of the binding of [3H]quinuclidinyl benzilate to the muscarinic receptors and for the inhibition of alpha-amylase secretion. The KB values determined by the guinea-pig ileum assays were approximately 10(-5) to 10(-6) M. The ranking of antimuscarinic potency of the compounds in the three different assays were in good agreement.
在三种胆碱能系统生物学试验中测定了羟氨喹及其五种抗血吸虫类似物的抗毒蕈碱活性。在小鼠中，羟氨喹类似物的半数致死量（LD50）值与以下各项之间建立了线性关系：1）通过抑制[3H]喹核醇基苯甲酸酯与N4TG1神经母细胞瘤细胞毒蕈碱受体结合获得的抑制常数（Ki）值；2）通过抑制卡巴胆碱诱导的胰腺腺泡细胞α淀粉酶分泌获得的半数抑制浓度（I50）值；3）通过抑制乙酰胆碱诱导的豚鼠回肠收缩获得的平衡解离常数（KB）值。抗毒蕈碱效力与小鼠毒性之间建立的线性关系表明，羟氨喹类似物的毒性与其抗毒蕈碱活性之间可能存在关联。另一方面，抗血吸虫效力与抗毒蕈碱效力之间未建立相关性。对于抑制[3H]喹核醇基苯甲酸酯与毒蕈碱受体结合以及抑制α淀粉酶分泌，Ki和I50值范围为10^(-7)至10^(-5)M。通过豚鼠回肠试验测定的KB值约为10^(-5)至10^(-6)M。在三种不同试验中，化合物的抗毒蕈碱效力排名高度一致。
