Comparison of the isolated human and guinea pig gallbladder strip models in the assessment of antispasmodic drugs

The objective of this study,vas to compare the antispasmodic activities of atropine, verapamil, (-)scopolamine n-butyl bromide and propinox iii the is olated human and guinea pig gallbladder strip models. Concentration-respons e curves for each of the the agents were obtained in both models following administration of carbachol. Atropine was the only drug to show marked acti vity in the guinea pig gallbladder model (ED50 = 2.75 x 10(-7) M); the rema ining drugs elicited less inhibition of a similar order of magnitude (ED50 = 1.65 x 10(-5), 4.18 x 10(-6) and 2.71 x 10(-5) M for verapamil, [-]scopol amine n-butyl bromide and propinox, respectively). In contrast, results obt ained from the human gallbladder strip model revealed differences among the drugs (ED50 = 5.03 x 10(-8), 1.34 x 10(-6), 6.63 x 10(-6) and 5.45 x 10(-5 ) M for atropine, propinox, verapamil and [-]scopolamine n-butyl bromide, r espertively). Based on these results, propinox showed a relative potency in the human gallbladder that was 20.22-fold higher than that in rite guinea pig model followed by atropine (5.47-fold) and verapamil (2.49-fold), where as (-)scopolamine n-butyl bromide was 0.07 rimes more potent in the guinea pig model. Regression analysis of ED50 values showed a lack of correlation between the two models (r = 0.44). Considering interspecies variations, fur ther studies in human tissues are needed to evaluate the efficacy of antisp asmodic drugs. (C) 1999 Prous Science. All rights reserved.