Alpha-aminoamide Sodium Channel Blockers for Bladder Overactivity

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Solution Overview

Problem

Current treatments for lower urinary tract disorders such as overactive bladder, prostatitis, interstitial cystitis, benign prostatic hyperplasia, and urinary incontinence have limited efficacy and are associated with significant side effects, necessitating the development of more effective therapies.

Innovation Solution

The use of α-aminoamide derivatives as sodium channel blockers to treat lower urinary tract disorders by modulating ion channels and reducing bladder overactivity and urgency, with specific compounds like NW-1029 and NW-1099 being tested for their efficacy in animal models of bladder irritation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for lower urinary tract disorders are used, then some therapeutic effect is achieved, but side effects increase and efficacy is limited

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the pharmacological parameter by switching from antimuscarinic mechanism to sodium channel blocking mechanism. This fundamental parameter change in the therapeutic approach allows achieving bladder relaxation and reduced urgency through a different physiological pathway, potentially avoiding the side effects associated with antimuscarinic drugs such as dry mouth, constipation, and cognitive impairment.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent substitutes the mechanical/pharmacological system by replacing antimuscarinic drugs with compounds that block voltage-gated sodium channels. This substitution targets the neuronal excitability mechanism rather than the muscarinic receptor pathway, fundamentally changing how bladder overactivity is controlled and avoiding the harmful effects of the previous system.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If sodium channel blockers are used to suppress micturition reflex, then the volume threshold for bladder activation increases, but the mechanism of action must be precisely targeted to avoid side effects

Engineering Contradiction:

Improvebladder overactivity controlVSAvoidmechanism complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies local quality by designing sodium channel blockers with specific affinity for neuronal sodium channels in the bladder sensory pathways. The compounds are tailored to act locally on the afferent neurons involved in the micturition reflex, increasing the volume threshold for activation without affecting sodium channels in other parts of the body, thereby controlling bladder overactivity with targeted precision.

Inventive Principle:

Principle #3Local quality

3Ease of operation

If existing therapies are administered, then some symptom relief is provided, but treatment limitations and inadequate efficacy persist

Engineering Contradiction:

Improvesymptom reliefVSAvoidtreatment efficacy

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent applies inversion by reversing the conventional approach to treating overactive bladder. Instead of using antimuscarinic drugs that block acetylcholine receptors, the invention uses sodium channel blockers that prevent action potential propagation in sensory neurons. This inverted pharmacological strategy addresses the underlying neuronal hyperexcitability rather than just blocking the final effector pathway, providing more reliable symptom relief.

Inventive Principle:

Principle #13The other way round (Inversion)

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 α-aminoamide derivatives effectively increase the volume threshold for bladder activation, reducing symptoms of bladder overactivity and urgency, and show promise in treating various lower urinary tract disorders with potentially fewer side effects compared to existing treatments.

Implementation Method 1

α-aminoamide derivatives useful in the treatment of lower urinary tract disorders... a chemical class of sodium channel blockers... modulating ion channels, would be expected to increase the volume threshold for activation of the micturition reflex

Methodology Applied

Scientific EffectSodium channel blocking: Conduction (electrical)

Data Source

PatentUS7718815B2Alpha-aminoamide derivatives useful in the treatment of lower urinary tract disorders

Publication Date: 2010.05.18 NEWRON PHARMACEUTICALS SPA

AI summary

Methods of using certain α-aminoamide derivatives to treat lower urinary tract disorders. The therapeutic agents of the invention are able to reduce or even stop the lower urinary tract disorders substantially without side effects.