Monoamine Transporter Modulators via Allosteric Binding
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Solution Overview
Problem
Current therapies for brain-related disorders involving aberrant monoamine signaling lack specificity and often come with side effects, as they interfere with the normal reuptake of endogenous neurotransmitters or have psychostimulant properties.
Innovation Solution
Development of novel compounds that modulate the activity of monoamine transporters without interfering with their normal reuptake, using specific allosteric binding sites to induce conformational changes and regulate transporter function, thereby treating or preventing brain-related diseases without side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional therapies targeting monoamine transporters are used to treat brain-related disorders, then therapeutic effects are achieved, but side effects occur due to interference with normal neurotransmitter reuptake
Solution Approach 1:
The patent applies local quality by designing compounds that selectively bind to specific conformational states of monoamine transporters (e.g., outward-open vs inward-open states) rather than blocking all states. This allows modulation of pathological processes while preserving normal physiological reuptake functions, thereby achieving therapeutic effects without interfering with normal neurotransmitter clearance
Solution Approach 2:
The invention changes the binding parameters of transporter modulators by targeting specific conformational states through allosteric sites or state-dependent orthosteric sites. This parameter change enables selective modulation of transporter activity in pathological conditions while maintaining normal function in healthy states, reducing side effects
2Ease of operation
If psychostimulants are used to treat brain-related disorders, then symptom relief is achieved, but abnormal psychostimulant properties and abuse potential arise
Solution Approach 1:
The patent segments the transporter function into distinct conformational states (outward-open, inward-open, occluded) and develops modulators that selectively target specific states. This segmentation allows therapeutic intervention in pathological states without producing the non-selective psychostimulant effects that lead to abuse potential
Solution Approach 2:
The invention introduces allosteric modulators as intermediaries that bind to sites distinct from the primary neurotransmitter binding site. These allosteric modulators indirectly influence transporter function and neurotransmitter release, providing therapeutic effects without directly activating psychostimulant pathways that cause abuse potential
Data Source
AI summary
The present invention provides compounds useful for treating or preventing a brain-related disease or disorder. The present invention further provides a method of treating or preventing a brain-related disease or disorder in a patient, comprising administering to the patient a pharmaceutical composition comprising at least one compound of the invention. The present invention further provides a method of modulating the activity of a monoamine transporter.