Uncovering Structure-Activity Relationships of Phenethylamines: Paving the Way for Innovative Mental Health Treatments.
Sedat Karabulut, Harpreet Kaur, James W Gauld
ACS Chemical Neuroscience February 21, 2024 DOI: 10.1021/acschemneuro.3c00677 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Computational QSAR modeling study Peer reviewed |
|---|---|
| Population | Phenethylamine compounds and their interactions with monoamine transporters (serotonin, dopamine, and norepinephrine transporters) |
| Key points | The authors report that three QSAR models predicting phenethylamine inhibition of serotonin, dopamine, and norepinephrine reuptake were validated across fitting, internal, and external criteria, with external R2 values of 0.955 for the serotonin transporter, 0.831 for the dopamine transporter, and 0.711 for the norepinephrine transporter. They propose these models as tools for developing new therapeutic modalities. |
Abstract
The rapidly evolving psychedelic industry has garnered considerable attention due to 3,4-methylenedioxymethamphetamine-assisted psychotherapy's ground-breaking success in treating moderate-to-severe Post-traumatic Stress Disorder in two Phase 3 clinical trials. This has opened Pandora's box for the development of innovative therapeutic modalities. Of particular interest are the phenethylamines and their ability to inhibit monoamine transporters. In this study, we employed the quantitative structure-activity relationship methodology to develop three vigorous models for the reuptake of serotonin, dopamine, and norepinephrine through monoamine transporters. These models were thoroughly validated using various criteria, including fitting (R2DAT = 0.869, R2SERT = 0.828, and R2NET = 0.887), internal (Q2looDAT = 0.795, Q2looSERT = 0.784, and Q2looNET = 0.820), and external (RMSEextDAT = 0.373, R2extDAT = 0.831, RMSEextSERT = 0.200, R2extSERT = 0.955, RMSEextNET = 0.318, and R2extNET = 0.711) criteria.