オバラ　ケイスケ   Obara Keisuke   小原　圭将    所属   東邦大学  薬学部 薬学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Inhibitory effects of antidepressants on acetylcholine-induced contractions in isolated guinea pig urinary bladder smooth muscle
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	99(1-2),pp.89-98
著者・共著者	Uno J†, Obara K†, Suzuki H†, Miyatani S†, Chino D†, Yoshio T†, Tanaka Y＊†
担当区分	2nd著者
発行年月	2017/01
概要	Background/Aims: To investigate the potential inhibitory effects of 18 clinically available antidepressants on acetylcholine (ACh)-induced contractions in guinea pig urinary bladder smooth muscle (UBSM) in order to predict whether they may induce voiding impairment. Methods: Concentration-response curves for ACh-induced contractions in guinea pig UBSM strips were obtained in the absence or presence of selected antidepressants. When inhibitory effects indicated competitive antagonism, pA2 values against ACh were calculated and compared to plausible antidepressant blood concentrations. Results: ACh-induced contraction was antagonized competitively within clinical dose ranges by tricyclic antidepressants (imipramine, amitriptyline, trimipramine, clomipramine, nortriptyline, and amoxapine), maprotiline (a tetracyclic antidepressant), and mirtazapine (a NaSSA). ACh-induced contraction was also significantly inhibited by mianserin (a tetracyclic antidepressant), paroxetine and sertraline (SSRIs), and duloxetine (an SNRI), albeit at concentrations that substantially exceeded clinically achievable blood levels. However, ACh-induced contractions were not significantly affected by fluvoxamine and escitalopram (SSRIs), milnacipran (an SNRI), trazodone (a serotonin 5-HT2A receptor antagonist), sulpiride (a dopamine D2 receptor antagonist), or aripiprazole (a dopamine partial agonist). Conclusion: These findings suggest that, in addition to tricyclics, some relatively novel antidepressants such as mirtazapine can induce voiding impairment, attributed to diminished UBSM contractility from the inhibition of muscarinic receptors in the UBSM.