EFFECTS OF VAMICAMIDE ON URINARY-BLADDER FUNCTIONS IN CONSCIOUS DOG AND RAT MODELS OF URINARY FREQUENCY

Purpose: To investigate the usefulness of vamicamide, (+/-)-(2R, -4-d imethylamino-2-phenyl-2-(2-pyridyl)valeramide, as a novel drug for the treatment of urinary frequency and incontinence. Materials and Method s: Urinary frequency was evaluated in specially devised conscious dog and rat models by investigating the effects of the drug on urinary bla dder function of these animals by cystometrography. Results: In the do g model with transected hypogastric nerves, the bladder volume at mict urition (bladder capacity) was less than 50% that of the sham-operated dog, and in the rat model with bilateral lesioning of nuclei basalis, a part of the brain, by ibotenic acid injection, bladder capacity was about 50% that of the sham-operated rat. Other bladder functions in b oth models were unchanged. In the dog model, orally administered vamic amide at 0.32 and 1.0 mg./kg. significantly increased bladder capacity and did not change residual urine volume or micturition pressure. Oxy butynin 0.10 mg./kg., one of the most popular drugs for the treatment of urinary frequency and incontinence, or atropine 0.10 mg./kg. induce d significant increases in bladder capacity similarly to vamicamide at 0.32 mg./kg. In the rat model, oral vamicamide 0.32 mg./kg. also sign ificantly increased bladder capacity and did not change micturition pr essure or threshold pressure. Again, oxybutynin 0.10 mg./kg. or atropi ne 0.32 mg./kg. had almost the same effects as vamicamide 0.32 mg./kg. Conclusions: These findings suggest that vamicamide should be useful for the treatment of urinary frequency.