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	The recovery effects of distigmine on guinea pig detrusor underactivity induced by anticholinergic drugs
掲載誌名	正式名：Pharmacometrics
出版社	応用薬理研究会
巻・号・頁	91(1/2),pp.25-39
著者・共著者	Obara K†, Chino D†, Tanaka Y＊†
担当区分	筆頭著者
発行年月	2016/07
概要	The present study was carried out to obtain experimental evidence that distigmine significantly restores the detrusor underactivity produced by anticholinergic drugs. Inhibitory effects of atropine and imipramine on acetylcholine (ACh)-induced contraction of isolated guinea pig urinary bladder smooth muscle (UBSM) in vitro and UB pressure changes measured by cystometry in vivo were examined. Restorative effects of distigmine and bethanechol on atropine- and imipramine-produced inhibition were also examined. The in vitro studies showed that atropine (3 × 10-9–3 × 10-8 M) and imipramine (3 × 10-7–3 × 10-6 M) competitively inhibited ACh-induced contraction. ACh-induced contractions suppressed by atropine (10-8 M) and imipramine (10-6 M) were significantly restored by distigmine (3 × 10-7 M). Atropine (0.3 mg/kg, i.v.) and imipramine (30 mg/kg, i.v.) significantly decreased maximum intravesical pressure (IVPmax) for 4 h during micturition reflex in vivo and significantly increased post-voiding residual urine volume. Both parameters were largely restored by distigmine (0.03 mg/kg, i.v.). For bethanechol, significant recovery effects were observed for IVPmax decreased by atropine or imipramine (3.0 mg/kg or 0.1 mg/kg (i.v.), respectively). However, the effect of bethanechol on increased residual urine volume was not significant in either case. Distigmine significantly restored UB contractile functions decreased by anticholinergic drugs, to an extent that appears superior to bethanechol according to the evidence found in this study.