Abstract
3.3%). The potency of solabegron was also significantly increased in the presence of both oxybutynin and tolterodine with IC50 values of 0.05 M and 0.03 M, respectively, versus vehicle (0.14 M). The efficacy of CL-316,243 was also significantly increased in the presence of oxybutynin and tolterodine, (Emax values of 84.7 2.7% and 91.3 1.5%, respectively) compared to vehicle (Emax 68.6 3.0%). However, the potency of CL-316,243 was only significantly affected in the presence of oxybutynin (IC50 value of 1.91 nM compared with 7.36 nM for vehicle). In the presence of oxybutynin, tolterodine or solifenacin, the potency of mirabegron was significantly increased with IC50 values of 0.87 M, 0.33 M and 0.77 M, respectively versus vehicle (1.71 M), while no significant effects on efficacy were observed. CONCLUSIONS: The current results demonstrate that the combination of antimuscarinics and 3-adrenoceptor agonists can result in increased efficacy and potency and supports the hypothesis that combining these compound classes in the clinic could have beneficial effects in treating urinary bladder dysfunction.
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