PT  - JOURNAL ARTICLE
AU  - Hiroshi Nagabukuro
AU  - Katherine L. Villa
AU  - L. Alexandra Wickham
AU  - Alison A. Kulick
AU  - Loise Gichuru
AU  - Marcie J. Donnelly
AU  - Gregory O. Voronin
AU  - Tony Pereira
AU  - Xinchun Tong
AU  - Andrew Nichols
AU  - Stephen E. Alves
AU  - Gary P. O'Neill
AU  - Christopher V. Johnson
AU  - Emily J. Hickey
TI  - Comparative Analysis of the Effects of Antimuscarinic Agents on Bladder Functions in Both Nonhuman Primates and Rodents
AID  - 10.1124/jpet.111.179747
DP  - 2011 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 220--227
VI  - 338
IP  - 1
4099  - http://jpet.aspetjournals.org/content/338/1/220.short
4100  - http://jpet.aspetjournals.org/content/338/1/220.full
SO  - J Pharmacol Exp Ther2011 Jul 01; 338
AB  - 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 nonhuman 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 (nonselective) and oxybutynin (moderately M3-selective) increased bladder capacity at lower doses than those required to decrease micturition pressure. However, higher doses of darifenacin (M3-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 of the 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 M3 receptor, other muscarinic receptor subtypes contribute to regulate bladder storage function in nonhuman primates, since less subtype-selective tolterodine and oxybutynin showed higher specificity to the bladder capacity effect than the effect on micturition pressure compared with M3-selective darifenacin. In addition, the role of muscarinic receptors in bladder storage function varies between primates and rodents. Compared with rodents, muscarinic receptors may play a more active role during the storage phase to regulate the functional bladder capacity in primates.