In vitro intravesical instillation of anticholinergic, antispasmodic and calcium blocking agents (rabbit whole bladder model)

Abstract

The systemic side effects accompanying oral pharmacotherapy of neurogenic bladder dysfunction present significant drawbacks to this type of therapy. In these studies we investigated the effect of intravesical administration of anticholinergic, antispasmodic and calcium blocking agents on pressure response mediated by field stimulation and bethanechol. We used the rabbit in vitro whole bladder model for these experiments. The bladder from a mature male NZW rabbit was mounted in an organ bath as a whole bladder preparation. After control field stimulation and bethanechol stimulation, 20 ml. of saline containing the specific drug being evaluated was instilled into the bladder. At 30 minute intervals, the responses to field stimulation and bethanechol were determined. Two hours after instillation of 100 microM of each specific drug, the inhibition of the contractile response to bethanechol and field stimulation (as % inhibition) was as follows: oxybutynin (95%/64%), verapamil (85%/81%), atropine (68%/31%), diltiazem (47%/39%), and imipramine (44%/47%). Atropine and oxybutynin suppressed the contractile response of the bladder to bethanechol to a much greater extent than that to field stimulation, while verapamil, diltiazem and imipramine suppressed the contractile response to bethanechol and field stimulation to approximately the same extent. Two hours after drug instillation, the intravesical solution was washed out and replaced with saline, but the recovery of the bladder contraction was slow and incomplete. The results of this study suggest that the use of self-intravesical instillation to suppress bladder contractility should be a good therapeutic approach for patients with neurogenic bladder, especially those who are already managed by intermittent catheterization.