Effects of drugs used in the therapy of detrusor hyperactivity on the volume-induced contractions of the rat urinary bladder.
In this study we examined the effects of the drugs most commonly utilized in the therapy of overactive detrusor, on the volume-induced contractions of rat urinary bladder. Anticholinergics such as propantheline bromide and emepronium bromide, as well as oxybutynin decreased the amplitude of the voiding contractions after intravenous (i.v.) administration in a dose-dependent way. These anticholinergics, on the other hand, generally increased the frequency of the contractions. Nifedipine dose-dependently reduced the amplitude of the contractions. Flavoxate induced a dose-related decrease in the frequency without effects on the amplitude of the peaks. Its main metabolite 3-methylflavone-8-carboxylic acid (MFCA) was inactive after i.v. administration. Terodiline was active on the amplitude and apparently on the frequency of the voiding contractions. The alpha-adrenoceptor antagonist prazosin, as well as indomethacin, inhibited only the frequency of the voiding contractions. All the drugs active in reducing the frequency of the voiding contractions after i.v. administration, proved effective also after intracerebroventricular (i.c.v.) injection. The model of the volume-induced contractions of rat urinary bladder, seems to be a useful tool to evaluate in vivo the effects of a compound on the bladder, allowing the possibility of distinguishing among antimuscarinics and calcium antagonists, which peripherally decrease bladder contractility, and other drugs inducing a decrease in the frequency of the voiding reflex acting on the micturition centre(s) in the central nervous system (CNS).
Guarneri
L
L
Pharmacology Department, Research Laboratories, Recordati S.p.A., Milan, Italy.
Ibba
M
M
Angelico
P
P
Colombo
D
D
Fredella
B
B
Testa
R
R
D000818:Animals; D005260:Female; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects*; D001745:Urinary Bladder Diseases / Q000188:drug therapy*; D014555:Urination Disorders / Q000188:drug therapy*; D014556:Urine / Q000502:physiology