Anton A H, Czinn S, Jazwa J, Tam L, Amaranath L
Res Commun Chem Pathol Pharmacol. 1978 Nov;22(2):375-83.
These results for the first time document that the brief duration of action of the ganglionic blocker, Arfonad (trimethaphan camsylate), is not due to inactivation by plasma cholinesterase. Inhibition of the enzyme in vitro by Arfonad was not altered by prior incubation of the drug in plasma at 37 degrees C for up to 16 hours nor by treatment with NaOH at 100 degrees C for 10 minutes. Both procedures inactivated succinylcholine. These results in vitro were confirmed in vivo by finding that the toxicity of Arfonad in mice was not significantly altered by these procedures whereas they rendered succinylcholine inocuous. Arfonad is a noncompetitive whereas succinylcholine is a competitive inhibitor of plasma cholinesterase using benzoylcholine as the substrate. The camphorsulfonate moiety of Arfonad was inactive in vitro but caused mild tremors in mice at relatively high doses.
这些结果首次证明，神经节阻断剂阿方那特（樟脑磺酸三甲铵）作用持续时间短暂并非由于被血浆胆碱酯酶灭活。在体外，将阿方那特在37℃的血浆中预孵育长达16小时，或在100℃用氢氧化钠处理10分钟，均不会改变该药对该酶的抑制作用。这两种处理方法均可使琥珀酰胆碱失活。通过发现以下情况，这些体外实验结果在体内得到了证实：这些处理方法并未显著改变阿方那特对小鼠的毒性，而它们却使琥珀酰胆碱变得无害。以苯甲酰胆碱为底物时，阿方那特是一种非竞争性抑制剂，而琥珀酰胆碱是血浆胆碱酯酶的竞争性抑制剂。阿方那特的樟脑磺酸盐部分在体外无活性，但在相对高剂量时会使小鼠出现轻度震颤。
