MAOI and 5-HT2A Agonist Combinations for Oral Bioavailability

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Solution Overview

Problem

Psychedelic compounds like DMT have variable bioavailability and rapid metabolic clearance, limiting their clinical use and requiring invasive administration routes, which undermines treatment accessibility and efficacy.

Innovation Solution

Combining a monoamine oxidase inhibitor (MAOI) such as CX157 with a serotonin 2A (5-HT2A) receptor agonist, including deuterated DMT, to enhance bioavailability and reduce degradation, allowing for safer and more accessible oral administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If DMT is administered orally, then treatment accessibility is improved, but rapid metabolic clearance reduces bioavailability and efficacy

Engineering Contradiction:

Improveoral administration accessibilityVSAvoidbioavailability

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent introduces a monoamine oxidase inhibitor (MAOI) as an intermediary substance that prevents the rapid metabolic clearance of DMT. The MAOI acts as a mediator between the oral administration route and the target serotonin receptors, blocking the enzyme (MAO) that would otherwise degrade DMT before it can reach its therapeutic target, thereby enabling reliable oral bioavailability.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the pharmacokinetic parameters of DMT by combining it with an MAOI. This parameter change involves altering the metabolic degradation rate of DMT from rapid clearance to sustained presence in the system. The MAOI modifies the enzyme-substrate interaction parameters, preventing the catabolic breakdown of DMT and thereby improving bioavailability while maintaining oral administration ease.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If DMT is administered via injection or inhalation, then bioavailability is improved, but administration complexity and invasiveness increase

Engineering Contradiction:

ImprovebioavailabilityVSAvoidadministration route complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The MAOI serves as a biochemical intermediary that enables the simple oral administration route to achieve the bioavailability typically requiring complex invasive routes. By blocking metabolic degradation at the molecular level, the MAOI allows oral intake to functionally equivalent to injection or inhalation in terms of therapeutic effect, while avoiding the complexity and invasiveness of those alternative routes.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Ease of operation

If DMT is administered orally without MAOI, then ease of administration is maintained, but rapid metabolic clearance reduces duration of action

Engineering Contradiction:

Improveoral administration simplicityVSAvoidduration of action

Core Design Contradiction:

Ease of operationVSDuration of action of moving object

Solution Approach 1:

The MAOI enables continuous presence of DMT in the system by preventing its metabolic degradation. Instead of DMT being rapidly cleared and needing repeated dosing, the MAOI creates a continuous action by blocking the degradation pathway. This allows the simple oral administration to maintain therapeutic levels throughout the desired duration, eliminating the need for frequent re-dosing while preserving ease of administration.

Inventive Principle:

Principle #20Continuity of useful action

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 combination increases the oral bioavailability and in vivo half-life of 5-HT2A receptor agonists, minimizing side effects and improving treatment accessibility and efficacy for disorders like depression and PTSD.

Implementation Method 1

Combining a monoamine oxidase inhibitor (MAOI) such as CX157 with a serotonin 2A (5-HT2A) receptor agonist, including deuterated DMT, to enhance bioavailability and reduce degradation

Methodology Applied

Scientific EffectMonoamine oxidase inhibition: Enzyme

Data Source

PatentUS20250248969A1Combinations of monoamine oxidase inhibitors and serotonin receptor agonists and their therapeutic use

Publication Date: 2025.08.07 REMEDI INC

AI summary

Disclosed are methods of treating a subject having a disease or disorder by administering a monoamine oxidase inhibitor in combination with a serotonin receptor agonist, which in some embodiments is a deuterated serotonin receptor agonist. In some aspects, the disclosure further relates to pharmaceutical compositions and kits comprising a monoamine oxidase inhibitor and a serotonin receptor agonist. In some embodiments, the monoamine oxidase inhibitor is a MAO-A-selective inhibitor such as CX157, and the serotonin receptor agonist is a serotonin 2A receptor agonist such as N,N-dimethyltryptamine (DMT), or deuterated DMT.