Inhibitory Effects of Tiropramide and Propiverine HCI against Smooth Muscle Contraction of Rat Urinary Bladder: In-vitro Muscle Strip Study

Yoon, Cheol Yong; Lee, Dong Soo; Lee, Jeung Gu

Abstract

AIMS OF STUDY: Present study designed to observe inhibitory effects of propiverine HC1 and tiropramide against the smooth muscle contraction of female rat bladder. Propiverine has both direct smooth muscle relaxation and anticholinergic effect and has relatively fewer side effect than conventionally used drugs such as oxybutinin. Tiropramide has been known as modulatory agents of gastrointestinal motility but also has inhibitory effects against the bladder contraction.
METHODS
30 adult female Sprague-Dawley rats were used. Bladder body above ureteral orifice was resected under pentobarbital anesthesia. 1 x 0.5 cm sized smooth muscle strip was made, and incubated in Tyrode`s solution aerated with 95% oxygen. After reaching equilibrium state, each strip was stimulated by field stimulation (FS, 1-32 Hz) and bethanechol administration (0.0000001-0.0001M). From each strip, degree of muscle contraction was recorded by physiograph (Gilson IC-MP). After the control stimulations, each strip was treated by atropine, tiropramide, oxybutinin and propiverine HC1. After 30 minutes, same stimulation were repeated and degree of muscle contraction was compared to pre incubation data.
RESULTS
Frequency and dose dependent muscle contractions were noted for both FS and bethanechol stimulation. Greater degree of contractions were noted for FS than for bethanechol stimulation. Inhibitory effects of tiropramide, propiverine HC1 and oxybutinin were greater than those of atropine at FS (1-32 Hz). At high concentration (0.0001M), all of the drugs but atropine inhibited field stimulated smooth muscle contraction more than 90%. At lower concentration (0. 0000001-0.000001M), inhibitory actions of oxybutinin and propiverine HC1 were greater than that of tiropramide (p>0.05). Propiverine HC1 and oxybutinin had similar inhibitory effect for all con-centration. At higher concentration (0.0001M), inhibitory effects of tiro-pramide were more than 98% whereas those of oxybutinin and propiverine HC1 were 88%. At low concentration (0.0000001-0.000001M), oxybutinin exhibited greater inhibition against the bethanechol induced contraction than did tiropramide and propiverine HC1. With these results, it was suggested that in low concentration, oxybutinin and propiverine HCI had greater inhibitory effect than did tiropramide against smooth muscle contraction of the bladder. In high concentration though, tiropramide had superior inhibitory effect than did oxybutinin and propiverine HC1. Since, no difference was noted between oxybutinin and propiverine HC1 for the inhibitory action of bladder contraction, propiverine HC1 seems reasonable substitute for the treatment of detrusor hyperreflexia with less side effects. Also these results indicate that tiropramide can be used for the management of unstable bladder.