Filamin A Binding Compound Prevents Opioid Tolerance

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Solution Overview

Problem

Current opioid therapies face challenges with analgesic tolerance, dependence, and addiction due to chronic opioid-induced switches in G protein coupling by mu opioid receptors, leading to undesirable adaptive responses.

Innovation Solution

A compound that binds to filamin A with high affinity, preventing the Gi/o-to-Gs coupling switch of mu opioid receptors, thereby reducing inflammation and preserving analgesic effects while minimizing tolerance and addictive properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If chronic opioid administration is used to maintain analgesic effects, then pain relief is sustained, but analgesic tolerance and dependence develop due to G protein coupling switch

Engineering Contradiction:

Improveduration of analgesic effectVSAvoidanalgesic tolerance and dependence

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The patent introduces filamin A as an intermediary protein that mediates the interaction between mu opioid receptors and Gs proteins. By binding to filamin A, the compound prevents the harmful MOR-Gs coupling pathway while allowing the beneficial MOR-Gi/o coupling to persist, thus maintaining analgesia without inducing tolerance or dependence

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention segments the G protein coupling pathways by selectively targeting the Gs coupling pathway through filamin A binding, while preserving the Gi/o coupling pathway. This segmentation allows differential modulation of opposing signaling cascades, maintaining analgesic effects without the harmful adaptive responses

Inventive Principle:

Principle #1Segmentation

2Object-affected harmful factors

If mu opioid receptor agonists are administered to achieve analgesia, then pain relief is provided, but inflammatory responses are exacerbated due to Gs protein coupling

Engineering Contradiction:

Improveinflammatory responseVSAvoidanalgesic efficacy

Core Design Contradiction:

Object-affected harmful factorsVSEase of operation

Solution Approach 1:

The patent converts the harmful inflammatory response caused by MOR-Gs coupling into a beneficial effect by using the same filamin A binding mechanism to selectively block this pathway. The compound binds to filamin A with high affinity, preventing the pro-inflammatory Gs coupling while preserving the analgesic Gi/o coupling, thus turning a harmful side effect into a therapeutic advantage

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

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 compound provides long-lasting analgesia with reduced risk of analgesic tolerance and dependence, maintaining opioid receptor function and reducing inflammatory responses.

Implementation Method 1

A compound that binds to filamin A with high affinity, preventing the Gi/o-to-Gs coupling switch of mu opioid receptors

Methodology Applied

Scientific EffectMolecular binding:

Data Source

PatentUS9340558B2Filamin a binding anti-inflammatory and analgesic

Publication Date: 2016.05.17 PAIN THERAPEUTICS INC

AI summary

A compound or its pharmaceutically acceptable salt, optionally including both individual enantiomeric forms, a racemate, diastereomers and mixtures thereof, composition and method are disclosed that can provide analgesia and reduce inflammation. A contemplated compound has a structure that corresponds to Formula A, wherein the R group substituents, d, e, f, k, n, m, D, E, F, K, G, P, Q, W, and Z are defined within.