Different responses to drugs against overactive bladder in detrusor muscle of pig, guinea pig and mouse.
Direct comparison of experimental data for drugs commonly used in the treatment of overactive bladder is difficult because of possible species differences. In this study, we compare the effects of atropine, propiverine, oxybutynin and tolterodine in strips of pig, guinea pig and mouse detrusor muscle. In the three species, we observed slight differences in potency of carbachol-induced biphasic contractile responses between the species (guinea pig>pig>mouse). Cumulative concentration-response curves for carbachol were shifted to the right by atropine, propiverine, oxybutynin and tolterodine. However, at higher concentrations of the latter three antagonists, the maximum response to carbachol was also reduced. Therefore, propiverine, oxybutynin and tolterodine must have additional pharmacological actions beyond competitive antagonism at muscarinic receptors. Electric field stimulation (30 Hz) of detrusor strips led to contraction amplitudes, which remained constant over time (210 min) in pig, decreased by 17+/-5% in guinea pig, and increased by 28+/-9% in mouse detrusor muscle. Electric field stimulation-evoked contractions were suppressed to 18% of pre-drug control by high concentrations of atropine (10 microM) in pig, but to a much lesser extent in guinea pig and mouse (to 46% and 70%, respectively). In all three species, a myogenic component of contraction was observed in the presence of tetrodotoxin (1 microM). Compared to atropine, the bladder spasmolytic agents propiverine, oxybutynin and tolterodine also reduced electrically evoked contractions in the three species, though higher concentrations were required. The differences in the reported effects of the spasmolytic agents commonly used for treating overactive bladder suggest that drug action is strongly dependent on the species. Thus, a comparison of drug effects is only feasible in the same animal model and the results cannot easily be transferred to humans.
Wüst
Melinda
M
Institute of Pharmacology and Toxicology, Faculty of Medicine, Dresden University of Technology, Fetscherstrasse 74, Dresden D-01307, Germany.
Averbeck
Beate
B
Reif
Silke
S
Bräter
Manfred
M
Ravens
Ursula
U
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001561:Benzilates / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D003408:Cresols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010665:Phenylpropanolamine; D013045:Species Specificity; D013552:Swine; D000068737:Tolterodine Tartrate; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D001559:Benzhydryl Compounds; D001561:Benzilates; D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D003408:Cresols; D008333:Mandelic Acids; D010665:Phenylpropanolamine; C015586:propiverine; D000068737:Tolterodine Tartrate; D001285:Atropine; D002217:Carbachol; C005419:oxybutynin