Discovery and <i>In Vitro</i> Characterization of SPL028: Deuterated <i>N</i>,<i>N</i>-Dimethyltryptamine.
Abstract
The psychedelic <i>N</i>,<i>N</i>- 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 (<i>N</i>,<i>N</i>-D<sub>2</sub>-dimethyltryptamine, D<sub>2</sub>-DMT) demonstrated the longest half-life and intrinsic clearance in hepatocyte mitochondrial fractions when compared with DMT. The <i>in vitro</i> receptor binding profile of D<sub>2</sub>-DMT was comparable to that of DMT, with the highest affinity at the 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>2C</sub> receptors. D<sub>2</sub>-DMT was therefore the preferred candidate to consider for further evaluation.
Topics & conditions
Detected automatically by Psychedelic Commons from the title and abstract, not labels from the source. They may be incomplete.
Psychedelic Commons aggregates metadata from open sources and links back to the original. Rights remain with the authors and publishers. Something wrong with this record? Report a problem.