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 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 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 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 M3-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.
- Received January 21, 2011.
- Revision received March 30, 2011.
- Accepted March 30, 2011.
- The American Society for Pharmacology and Experimental Therapeutics