Mechanisms of the suppression of the bladder activity by flavoxate.
BACKGROUND
This study was designed to clarify the primary site of action of flavoxate, clinically used for the treatment of urinary frequency.


METHODS
In rats, the effect of flavoxate on contractile responses in isolated detrusor strips, bladder contraction induced by pelvic nerve stimulation, isovolumetric rhythmic bladder contractions, and pelvic nerve activity were examined. In decerebrated cats, flavoxate was microinjected into the nuclei in the pons, and its effect on reflex micturition was observed.


RESULTS
Flavoxate suppressed carbachol- and calcium ion (Ca2+)-induced contractions of isolated detrusor strips in a noncompetitive and a competitive manner, respectively. Intravenous flavoxate suppressed both initial phasic, and later tonic, bladder contractions induced by electrical stimulation of the distal end of the pelvic nerve. It abolished isovolumetric rhythmic bladder contractions and the associated efferent pelvic nerve activity, without affecting baseline vesical pressure and afferent pelvic nerve activity. When administered intracerebroventricularly or intrathecally, it abolished isovolumetric rhythmic bladder contractions. Flavoxate microinjected into the nucleus reticularis pontis oralis (PoO; pontine micturition inhibitory region) of decerebrated cats inhibited the reflex micturition, but had no effect when microinjected into the locus coeruleus alpha (pontine micturition center) or locus subcoeruleus (pontine urine storage center).


CONCLUSIONS
Flavoxate suppressed the micturition reflex primarily by facilitating the inhibitory action of the PoO on the descending pathways from the pontine micturition center to the sacral parasympathetic intermediolateral nuclei.
Kimura
Y
Y
Discovery Research Laboratories I, Nippon Shinyaku Co. Ltd., Kyoto, Japan.
Sasaki
Y
Y
Hamada
K
K
Fukui
H
H
Ukai
Y
Y
Yoshikuni
Y
Y
Kimura
K
K
Sugaya
K
K
Nishizawa
O
O
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002415:Cats; D004558:Electric Stimulation; D005260:Female; D005422:Flavoxate / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D008845:Microinjections; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009476:Neurons, Efferent / Q000187:drug effects / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology; D010525:Peripheral Nerves / Q000166:cytology; D011149:Pons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013681:Tegmentum Mesencephali / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*; D014554:Urination / Q000187:drug effects
D010276:Parasympatholytics; D010277:Parasympathomimetics; D005422:Flavoxate; D001285:Atropine; D002217:Carbachol; D002118:Calcium