Comparison of various spasmolytic drugs on guinea-pig isolated common bile duct

Guinea-pig common bile duct preparations were used to quantify the spasmolytic potency of N-butylscopolamine (NBS), papaverine, gallopamil and nifedipine. A method was developed which allowed the measurement of intraluminal pressure changes in vitro. Barium chloride, carbachol and a solution with elevated potassium concentrations were used to stimulate smooth muscles. Concentration-response relationships for the spasmogens as well as for the spasmolytic drugs were evaluated in a cumulative manner. Furthermore, non-cumulative concentration-response curves were constructed for carbachol in the absence and presence of NBS. The -log EC50-values of the spasmogens were found to be 3.28 +/- 0.08 (BaCl2), 6.46 +/- 0.07 (carbachol) and 1.31 +/- 0.08 (KCl), respectively. The Emax values of carbachol and potassium were comparable, and were twice as high as the Emax of BaCl2. Papaverine was less potent than the calcium antagonists gallopamil and nifedipine, but proved capable of completely suppressing elevated muscular tone of the common bile duct preparation, independent of the stimulus used. NBS showed a high potency in suppressing only a carbachol-induced pressure increase, while it was rather ineffective when BaCl2 or a high potassium solution was used as the spasmogen. The concentration-response-curve for carbachol was shifted to the right in a parallel manner by NBS. Only a slight depression of Emax was observed. From the results it is concluded that NBS acts mainly as a muscarinic receptor antagonist. The high potency found for the calcium antagonists, gallopamil and nifedipine, in this model may indicate a possible role for these compounds in the treatment of biliary colic.