Exploring Endogenous Tryptamines: Overlooked Agents Against Fibrosis in Chronic Disease? A Narrative Review
Livers December 27, 2024 Hunter W. Korsmo
N-dimethylated tryptamines, including DMT and 5-MeO-DMT, are naturally produced in humans and other species. Once considered illicit, they are now being studied for mental health benefits. The enzyme INMT methylates tryptamine, which can activate SIGMAR1, a pro-survival pathway. In fibrogenic diseases like MAFLD, MASH, and CKD, INMT and SIGMAR1 activity changes as disease progresses. Endothelial cells and fibroblasts express INMT, but tryptamines' role in fibrosis is poorly understood. This review covers INMT's biochemistry and role in liver fibrosis, discusses preclinical and clinical findings on N-methylated tryptamines, highlights new therapeutic strategies for fibrogenic diseases, and mentions gut bacteria's influence on endogenous tryptamine signaling.