Bladder Smooth Muscle ATPase Inhibition for Overactive Bladder Control
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Solution Overview
Problem
Current treatments for overactive bladder, such as anti-muscarinic drugs, have limited efficacy and are plagued by intolerable side effects, making them ineffective for many patients due to unpredictable responses in smooth muscle and genetic changes with aging.
Innovation Solution
Administration of Myosin II ATPase inhibitor compounds, specifically substituted 3a-hydroxy-1-phenyl-1,2,3,3a-tetrahydro-4H-pyrrolo[2,3b]quinolin-4-one compounds, which inhibit Myosin II ATPase, either alone or in combination with PDE5 inhibitors or antimuscarinic drugs, to directly target the bladder muscle, reducing contractions and improving bladder control.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-muscarinic drugs are administered to block excessive acetylcholine binding, then the efficacy in treating overactive bladder symptoms is improved, but intolerable side effects such as blurred vision, dry mouth and constipation occur
Solution Approach 1:
The patent extracts the harmful side effects by switching from anti-muscarinic mechanism to Myosin II ATPase inhibition mechanism. The new compounds specifically target smooth muscle contraction through a different biochemical pathway, eliminating the side effects associated with acetylcholine receptor blockade while maintaining therapeutic efficacy for overactive bladder symptoms
Solution Approach 2:
The patent changes the therapeutic parameter from blocking acetylcholine receptors to inhibiting Myosin II ATPase activity. This fundamental mechanism change alters the biochemical pathway targeted, achieving the same therapeutic goal (reducing bladder contractions) without the harmful side effects of the previous approach
2Reliability
If anti-muscarinic drugs are used to treat overactive bladder, then some symptom relief is achieved, but about 75% of patients discontinue treatment due to intolerable side effects
Solution Approach 1:
The patent removes the cause of treatment discontinuation (intolerable side effects) by using a completely different mechanism of action. The Myosin II ATPase inhibitor compounds achieve symptom relief without the anticholinergic side effects that cause 75% of patients to stop treatment, thereby improving treatment continuation rates
3Reliability
If current pharmaceutical therapies are used to modify the myogenic pathway of bladder smooth muscle, then some effect on detrusor muscle contraction is achieved, but the response is unpredictable due to changes in genetic expression during development and aging
Solution Approach 1:
The patent targets a specific enzymatic parameter (Myosin II ATPase activity) that is more conserved and less subject to genetic expression changes compared to receptor systems. By focusing on enzyme inhibition rather than receptor blockade, the therapy achieves more predictable and consistent responses across different patient populations including the aging population
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The use of Myosin II ATPase inhibitor compounds effectively reduces the frequency and urgency of urination, enhances voluntary bladder control, and increases urination volume, providing a more tolerable treatment option for overactive bladder symptoms.
Implementation Method 1
Myosin II ATPase inhibitor compounds, including substituted 3a-hydroxy-1-phenyl-1,2,3,3a-tetrahydro-4H-pyrrolo[2,3b]quinolin-4-one compounds which in their active form can inhibit Myosin II ATPase
Data Source
AI summary
Provided are methods of treating an overactive bladder in a patient which include: administering a Myosin II ATPase inhibitor compound; or administering an X group and Y group substituted (3a-hydroxy-1-phenyl-1,2,3,3a-tetrahydro-4H-pyrrolo[2,3b] quinolin-4-one) compound of Formula 1 or administering an X group and Y group substituted (3a-hydroxy-1-phenyl-1,2,3,3a-tetrahydro-4H-pyrrolo[2,3b] quinolin-4-one) compound of Formula II; or administering pharmaceutically-acceptable salts, racemic mixtures, enantiomers, or prodrugs of said compounds, useful in their active form as inhibitors of Myosin II ATPase related to over-active bladder. Optionally the compounds are administered intervesicularly into the bladder. Also provided are pharmaceutical compositions comprising said compounds useful in their active form, as methods of treating a patient suffering from an over-active bladder related to inhibition of Myosin II ATPase. These pharmaceutical compositions also may contain one or more other compounds useful in their active form, as methods of treating a patient suffering from an over-active bladder.