Phenethylamine Prodrug Structures for Lower Side Effects
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Solution Overview
Problem
Phenethylamine and its derivatives have limited half-lives and cause significant side effects such as nausea and hypertension, making them unsuitable for widespread therapeutic use, especially in sensitive patients or those with cardiovascular conditions, and they can lead to rapid psychoactive effects and dependency.
Innovation Solution
Development of novel phenethylamine prodrugs with imine- and carbamate-structures that modify metabolic activity, reducing side effects and potential for abuse, while maintaining therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If phenethylamine or its derivatives are administered, then psychoactive effects are achieved, but side effects such as nausea and hypertension occur
Solution Approach 1:
The patent employs prodrugs as intermediary compounds that are converted to active phenethylamine in the body. These prodrugs (compounds of formula I) serve as mediators that deliver the psychoactive effect while reducing direct exposure to harmful metabolites, thereby minimizing side effects like nausea and hypertension
Solution Approach 2:
The patent modifies the chemical structure of phenethylamine by introducing substituent groups (R1-R5) and functional groups (X) to create prodrugs. These parameter changes in molecular structure alter pharmacokinetic properties, extending half-life and reducing metabolic inactivation while maintaining therapeutic efficacy
2Speed
If phenethylamine is administered, then rapid psychoactive effects are achieved, but potential for abuse and dependency increases
Solution Approach 1:
The prodrugs are designed to undergo preliminary metabolic conversion before releasing the active phenethylamine. This preliminary action of enzymatic conversion creates a controlled release mechanism that prevents rapid flooding of psychoactive compound in the organism, reducing abuse potential while maintaining therapeutic effect
Solution Approach 2:
The patent creates dynamically active prodrugs that convert to active compounds through metabolic processes. This dynamic conversion process controls the timing and rate of psychoactive compound release, preventing rapid onset that would indicate abuse while allowing therapeutic efficacy
3Reliability
If high dosage of mescaline is administered, then desired psychedelic state is achieved, but side effects like nausea and hypertension increase
Solution Approach 1:
The patent modifies mescaline's pharmacokinetic parameters through prodrug design, extending its half-life from minutes to hours. This parameter change allows achievement of therapeutic effect at lower dosages with prolonged duration, avoiding the need for high dosages that cause nausea and hypertension
Solution Approach 2:
The prodrugs provide sustained partial action over extended periods, eliminating the need for excessive dosing. The controlled conversion and release mechanism maintains therapeutic levels without requiring the large initial doses of mescaline that produce harmful side effects
Data Source
AI summary
The present invention relates to compounds according to formula (I), which are prodrugs of the psychoactive compound phenethylamine or its derivatives. The prodrugs provided herein exhibit improved pharmacokinetic properties during uptake as compared to phenethylamine (or the respective phenethylamine derivative), as well as reduced side effects resulting from the metabolites thus formed. Due to the affinity of the active phenethylamine compound, inter alia, for the 5-HT2a-receptor, these prodrugs are particularly advantageous for use in therapy, e.g., in the treatment of depression, posttraumatic stress disorder (PTSD), Alzheimer's disease or dementia.