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 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 最終著者,責任著者
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.