Document Detail

Comparative analysis of the effects of antimuscarinic agents on bladder functions in both non-human primates and rodents.
MedLine Citation:
PMID:  21459965     Owner:  NLM     Status:  Publisher    
Both the physiological role of muscarinic receptors for bladder function and the therapeutic efficacy of antimuscarinic agents for overactive bladder syndrome are well documented. We investigated the effect of antimuscarinic agents with different subtype selectivity on urodynamic parameters in non-human primates and rodents, and compared plasma levels of these agents between species. Anesthetized rhesus monkeys were transurethrally catheterized and the bladder was infused with saline. Urodynamic parameters were measured before and after intravenous drug administration. Tolterodine (non-selective) and oxybutynin (moderately M(3) selective) increased bladder capacity at lower doses than those required to decrease micturition pressure. However, higher doses of darifenacin (M(3) selective) were needed to increase the bladder capacity than those needed to decrease the micturition pressure. In rats, tolterodine had no effect on the bladder capacity, but decreased the micturition pressure at all doses administered. Oxybutynin also decreased micturition pressure and increased bladder capacity at the highest dose. Plasma levels of these drugs overlap in both species. These results suggest that, in addition to the M(3) recepetor, other muscarinic receptor subtypes contribute to regulate bladder storage function in non-human primates, since less-subtype selective tolterodine and oxybutynin showed higher specificity to the bladder capacity effect than the effect on micturition pressure, when compared to M(3)-selective darifenacin. Additionally, the role of muscarinic receptors in bladder storage function varies between primates and rodents. As compared to rodents, muscarinic receptors may play a more active role during the storage phase to regulate the functional bladder capacity in primates.
Hiroshi Nagabukuro; Katherine L Villa; L Alexandra Wickham; Alison A Kulick; Loise Gichuru; Marcie J Donnelly; Gregory O Voronin; Tony Pereira; Tong Xinchun; Andrew Nichols; Stephen E Alves; Gary P O'Neill; Christopher V Johnson; Emily J Hickey
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-1
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  -     ISSN:  1521-0103     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Merck Research Laboratories.
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