Recent advances in basic science for overactive bladder.
OBJECTIVE
Detrusor overactivity is a relatively common yet embarrassing symptom complex with significant impact on quality of life. The mainstay of current pharmacological treatment involves the use of muscarinic receptor antagonists, but their therapeutic effectiveness is limited by a combination of limited efficacy and troublesome side effects and has recently been challenged by Herbison et al. Recognition of the limitations of existing therapy has started the search for pharmacotherapeutic agents acting on alternative pathways underlying detrusor overactivity with the intention of improving storage symptoms of urgency, frequency and urge incontinence.


RESULTS
Recent research has suggested that several transmitters may modulate bladder storage. However, no agents currently available, acting via mechanisms other than muscarinic receptors have entered clinical practice so far. It is clear that far from being a passive container for urine, the urothelium is a crucial area within the bladder wall and its functions are complex and only now beginning to be appreciated. The release of several neurotransmitters from urothelium in response to distension and its action on receptors on sensory neurons is being increasingly recognized. The role for this afferent stimulation on the micturition reflex is gradually gaining importance in the pathophysiology of detrusor overactivity.


CONCLUSIONS
In this article, the recent developments in basic science related to the pathogenesis and pharmacological basis for future drug targets for effective management of overactive bladder are discussed.
Kumar
Vivek
V
Department of Urology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK. v.kumar@sheffield.ac.uk
Cross
Rebecca L
RL
Chess-Williams
Russell
R
Chapple
Christopher R
CR
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000503:physiopathology; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D001743:Urinary Bladder / Q000503:physiopathology*; D014549:Urinary Incontinence / Q000503:physiopathology*; D019459:Urothelium / Q000378:metabolism
D011976:Receptors, Muscarinic; D000255:Adenosine Triphosphate