The effect of darifenacin on overactive bladders in female and male rabbits.
Our current study utilized a model of bladder instability to compare the effectiveness of darifenacin, a selective m3 muscarinic antagonist, at inhibiting overactive bladder (OAB) dysfunction in both male and female rabbits. Twenty-four male and female NZ white rabbits were used for this experiment. Each rabbit was anesthetized and the carotid artery was cannulated for blood pressure (BP) monitoring and the left femoral artery was cannulated for acetylcholine (Ach) administration. The bladder dome was catheterized for monitoring bladder pressure and for cystometry. A ligature was placed around the urethra just distal to the bladder to induce OAB. After OAB developed, the response to four IV doses of darifenacin (0.003; 0.01; 0.03; 0.09 mg/kg) evaluated for their effects. Darifenacin: (1) was an equally potent inhibitor of the contractile response of both sexes to intra-arterial Ach, (2) had no effects on BP, (3) was a potent inhibitor of the frequency of OAB, but had a significantly less potent effect on the amplitude, and (4) Darifenacin showed a greater potency in the female rabbits than in the males. These studies provide support for the use of darifenacin in the treatment of OAB.
Levin
Robert M
RM
Stratton Veterans Affairs Medical Center, Albany, NY, USA. levinr@acp.edu
Juan
Yung-Shun
YS
Whitback
Catherine
C
Perez-Martinez
Franciso C
FC
Lin
Wei-Yu
WY
D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D009119:Muscle Contraction / Q000187:drug effects; D011759:Pyrrolidines / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D012737:Sex Factors; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
D001572:Benzofurans; D018727:Muscarinic Antagonists; D011759:Pyrrolidines; C101207:darifenacin