Coupet J, Fisher S K, Rauh C E, Lai F, Beer B
Eur J Pharmacol. 1985 Jun 7;112(2):231-5. doi: 10.1016/0014-2999(85)90500-x.
Amoxapine, an antidepressant with a rapid onset of therapeutic efficacy and great utility in psychotic depression, has been reported to produce anticholinergic side effects in man similar to those observed with imipramine and amitriptyline. To establish its cholinergic disposition, amoxapine and its metabolites 7-hydroxyamoxapine and 8-hydroxyamoxapine, have been evaluated by determining their effects on quinuclidinyl benzilate (QNB) binding to membrane fractions of rat and human brain, on the carbamoylcholine-stimulated accumulation of inositol phosphates in rat cerebral cortex and on the acetylcholine-induced contraction of the guinea pig ileum. In all three preparations, amoxapine was found to be a considerably weaker antagonist of muscarinic cholinergic receptors than either imipramine (4-27 fold) or amitriptyline (51-300 fold). These results indicate that for amoxapine, no correlation exists between the magnitude of muscarinic receptor inhibition and the extent of 'anticholinergic' side effects found in the clinic. Neither the metabolites of amoxapine nor species differences could account for this discrepancy.
阿莫沙平是一种起效迅速且对精神病性抑郁疗效显著的抗抑郁药，据报道，它在人体中产生的抗胆碱能副作用与丙咪嗪和阿米替林类似。为确定其胆碱能特性，通过测定阿莫沙平及其代谢产物7-羟基阿莫沙平和8-羟基阿莫沙平对大鼠和人脑膜部分中喹核醇基苯甲酸酯（QNB）结合的影响、对大鼠大脑皮层中氨甲酰胆碱刺激的肌醇磷酸积累的影响以及对豚鼠回肠乙酰胆碱诱导的收缩的影响，对它们进行了评估。在所有这三种制剂中，发现阿莫沙平作为毒蕈碱胆碱能受体拮抗剂的作用比丙咪嗪（4 - 27倍）或阿米替林（51 - 300倍）弱得多。这些结果表明，对于阿莫沙平，毒蕈碱受体抑制程度与临床发现的“抗胆碱能”副作用程度之间不存在相关性。阿莫沙平的代谢产物和物种差异均无法解释这种差异。
