CNS involvement in overactive bladder: pathophysiology and opportunities for pharmacological intervention

Area of Science:

• Neuroscience
• Pharmacology
• Urology

Background:

• Overactive bladder (OAB) pathophysiology is complex, involving peripheral and central nervous system (CNS) factors.
• CNS disorders like stroke and Parkinson's disease are linked to multifactorial OAB pathophysiology.
• Current first-line antimuscarinic drugs for OAB have limitations, necessitating alternative treatments.

Purpose of the Study:

• To explore novel therapeutic targets within the CNS for overactive bladder (OAB) treatment.
• To review the role of various CNS neurotransmitters in micturition control and their potential as drug targets.
• To assess the preclinical evidence for CNS-acting drugs in treating OAB and voiding disorders.

Main Methods:

• Review of existing literature on OAB pathophysiology and CNS involvement.
• Analysis of preclinical studies investigating the effects of drugs targeting CNS neurotransmitter systems on micturition.
• Examination of the potential of GABA, glutamate, opioid, serotonin, noradrenaline, and dopamine systems in OAB pharmacotherapy.

Main Results:

• Several CNS neurotransmitter systems, including GABA, serotonin (5-HT1A), opioids, and alpha-adrenoreceptors, show potential for modulating micturition and detrusor overactivity in preclinical models.
• Drugs targeting these CNS systems have demonstrated promising results in animal models of OAB.
• Limited human proof-of-concept studies exist for CNS-acting drugs in OAB treatment.

Conclusions:

• The CNS represents a promising area for developing new pharmacological treatments for overactive bladder (OAB).
• Targeting specific neurotransmitter systems within the CNS could offer alternatives to current therapies.
• Further human clinical trials are essential to validate the efficacy and safety of CNS-directed therapies for OAB.