Comparison of the isolated human and guinea pig gallbladder strip models in the assessment of antispasmodic drugs.
The objective of this study was to compare the antispasmodic activities of atropine, verapamil, (-)scopolamine n-butyl bromide and propinox in the isolated human and guinea pig gallbladder strip models. Concentration-response curves for each of the agents were obtained in both models following administration of carbachol. Atropine was the only drug to show marked activity in the guinea pig gallbladder model (ED50 = 2.75 x 10(-7) M); the remaining 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, [-]scopolamine n-butyl bromide and propinox, respectively). In contrast, results obtained 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, respectively). Based on these results, propinox showed a relative potency in the human gallbladder that was 20.22-fold higher than that in the guinea pig model followed by atropine (5.47-fold) and verapamil (2.49-fold), whereas (-)scopolamine n-butyl bromide was 0.07 times 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, further studies in human tissues are needed to evaluate the efficacy of antispasmodic drugs.
Baistrocchi
R
R
Instituto de Farmacología y Toxicología Roemmers, Hospital de Clínicas José de San Martín, Buenos Aires, Argentina.
de los Santos
A R
AR
Di Girolamo
G
G
Martí
M L
ML
Pico
J
J
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002764:Cholecystitis / Q000473:pathology; D005704:Gallbladder / Q000187:drug effects*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology
D010276:Parasympatholytics; D010277:Parasympathomimetics; D002217:Carbachol