Discovery and In Vitro Characterization of SPL028: Deuterated N,N-Dimethyltryptamine.
ACS medicinal chemistry letters – September 14, 2023
Source: PubMed
Summary
Scientists have discovered a modified version of DMT that lasts longer in the body while maintaining its therapeutic potential. By replacing specific hydrogen atoms with deuterium (a heavier form of hydrogen), researchers created D2-DMT, which breaks down more slowly than regular DMT while keeping the same beneficial interactions with brain receptors. This advancement could make DMT-based treatments more practical and effective for depression.
Abstract
The psychedelic N,N- dimethyltryptamine (DMT) is in clinical development for the treatment of major depressive disorder. However, when administered via intravenous infusion, its effects are short-lived due to rapid clearance. Here we describe the synthesis of deuterated analogues of DMT with the aim of prolonging the half-life and decreasing the clearance rate while maintaining similar pharmacological effects. The molecule with the greatest degree of deuteration at the α-carbon (N,N-D2-dimethyltryptamine, D2-DMT) demonstrated the longest half-life and intrinsic clearance in hepatocyte mitochondrial fractions when compared with DMT. The in vitro receptor binding profile of D2-DMT was comparable to that of DMT, with the highest affinity at the 5-HT1A, 5-HT2A, and 5-HT2C receptors. D2-DMT was therefore the preferred candidate to consider for further evaluation.