An overview of potassium channel activators for the treatment of overactive bladder: a survey of new structures 2000-2005

For over 25 years, the muscarinic receptor antagonists have been the first-line treatment for overactive bladder (OAb). However, severe dry mouth and exacerbation of disease symptoms with prolonged use can result in compliance rates as low as 30%. Approximately 10 years ago, investigators began to look for alternative approaches to the treatment of overactive bladder. in the recent past, it was demonstrated that ATP-dependent potassium channel openers designed as antihypertensive agents inhibited the hyperactivity associated with the symptoms of overactive bladder. Newer agents targeting other bladder potassium channels and/or bladder-specific channel subtypes represent an exciting new frontier for the effective treatment of OAB, with the potential of having an improved side effect profile compared to the antimuscarinic agents. In this review the authors examine the patent literature surrounding the discovery and development of several novel classes of compounds targeting the various potassium channels associated with urinary bladder activity and excitability. When appropriate, the primary literature is also touched upon to highlight pertinent structure-activity relationships (SAR) associated with these newly disclosed chemotypes.