Possible Mechanisms of Action of the Antispasmodic Agent Tiropramide in the Isolated Detrusor from Rats

The Japanese Journal of Pharmacology

Masatoshi Shirane¹  Koh-ichi Wada¹  Kouji Nagahamaya¹  Yutaka Matsuoka¹  Kazuhiko Kubota¹  Nobuyoshi Sunagane¹  Rieko Tsunematsu¹  Tsutomu Uruno¹ 

[1] Department of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo

关键词: Urinary bladder (rat);    Contraction;    Tiropramide;    Cytoplasmic free Ca2+;    Cyclic AMP;   

DOI  :  10.1254/jjp.60.275

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(15)Cited-By(4)The effects of tiropramide hydrochloride on Ca2+ induced contraction, cytoplasmic free Ca2+ levels and tissue cyclic AMP concentrations were investigated to elucidate the mechanisms of its antispasmodic action in the isolated detrusor from rats. Tiropramide inhibited the Ca2+ (3 mM)-induced contractions of the isolated urinary bladder depolarized in a Ca2+-free medium, and the IC50 value was 3.3 × 10-6 M. When tiropramide was added during the sustained phase of the K+ (60 mM)-contracture, IC50 values of tiropramide for the contraction and the increased fluorescence were 1.9 × 10-5 M and 16.4 × 10-5 M, respectively. On the other hand, the IC50 values for the K+-induced contraction and fluorescence after pretreatment of the isolated urinary bladder with tiropramide were 2.1 × 10-5 M and 2.6 × 10-5 M, respectively. Tissue cyclic AMP levels at 1 min after addition of 10-5 M tiropramide were significantly increased. Papaverine, IBMX or forskolin potentiated the inhibitory effect of tiropramide on carbachol-induced contraction and its cyclic AMP-elevating effect. However, a good correlation between the degrees of potentiation of the inhibitory effect and the increase in cyclic AMP levels was not observed. The present results suggest that the smooth muscle relaxant activity of tiropramide in the isolated detrusor from rats may be intimately associated with predominant inhibition of Ca2+ influx and, to a lesser extent, an increase in intracellular cyclic AMP levels.

【 授权许可】

Unknown