Discovery and In Vitro Characterization of SPL028: Deuterated N,N-Dimethyltryptamine.

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 high

SUBMITTER: Layzell M 

PROVIDER: S-EPMC10510671 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature