タナカ　ヨシオ   Tanaka Yoshio   田中　芳夫    所属   東邦大学  薬学部 薬学科    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Inhibition of recombinant human acetylcholinesterase activity by antipsychotics.
掲載誌名	正式名：Pharmacology 略　 称：Pharmacology ISSNコード：00317012/14230313
掲載区分	国外
出版社	Karger
巻・号・頁	104(1-2),pp.43-50
著者・共著者	Obara K＊†, Fujii A†, Arie C†, Harada N†, Yamaki F†, Matsuo K†, Yoshio T†, Tanaka Y†
担当区分	最終著者
発行年月	2019/05
概要	Background/Aims: Extrapyramidal symptoms (EPS) are representative side effects of antipsychotics, caused by their inhibitory action on dopaminergic nerves in nigrostriatal pathways. EPS could be also caused by direct augmentation of cholinergic effects, for example, by acetylcholinesterase (AChE) inhibition. We investigated the potential inhibitory effects of 26 clinically available antipsychotics on the activity of recombinant human AChE (rhAChE) to predict the role of antipsychotic-induced AChE inhibition in EPS onset. Method: The degree of rhAChE activity inhibition was calculated using the 5,5′-dithio-bis-(2-nitrobenzoic acid) method. Results: At a concentration of 10–5 mol/L, haloperidol, bromperidol, timiperone, nemonapride, pimozide, risperidone, blonanserin, aripiprazole, and brexpiprazole inhibited rhAChE activity by >20%. Risperidone, aripiprazole, and brexpiprazole inhibited rhAChE activity in a concentration-dependent manner, and their effects were more potent than those of other antipsychotics. The inhibitory effects of these 3 drugs were evident from 10–6 mol/L, and their pIC50 values were 4.74 ± 0.04, 4.80 ± 0.04, and 4.93 ± 0.06, respectively. Notably, the concentration range in which aripiprazole inhibited rhAChE activity (≥10–6 mol/L) overlapped with its clinically achievable blood levels. Conclusion: Aripiprazole may cause EPS at clinical dosages by augmenting cholinergic effects via AChE inhibition, in addition to its suppressive effect on dopaminergic neurons.
DOI	10.1159/000500227