Implications of Indolethylamine N-Methyltransferase (INMT) in Health and Disease: Biological Functions, Disease Associations, Inhibitors, and Analytical Approaches.
Seif Abouheif, Ahmed Awad, Christopher R Mccurdy
Brain Sciences August 28, 2025 DOI: 10.3390/brainsci15090935 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | DMT |
| Keywords | Inmt inhibitors Indolethylamine n-methyltransferase Neurotransmitter metabolism Sigma-1 receptor Inmt enzyme Drug discovery Disease mechanisms |
| Citations | 1 |
| Key findings | INMT is a promising but underexplored therapeutic target linked to neuropsychiatric disorders, neurodegeneration, and cancer. |
Abstract
Indolethylamine N-methyltransferase (INMT) is a Class 1 methyltransferase responsible for N-methylation of various endogenous and exogenous compounds, including tryptamine, serotonin, and dopamine. This review aims to provide a comprehensive overview of the biological and therapeutic relevance of INMT, emphasizing the human isoform (hINMT), highlighting its structural characteristics, disease association, and recent advances in analytical strategies. Dysregulation of INMT activity has been linked to a range of pathological conditions, including neuropsychiatric disorders, neurodegeneration, and several forms of cancer. These associations are addressed by integrating current findings across disease pathophysiology, enzyme inhibition, and analytical methodologies, including both radiolabeled and non-radiolabeled in vitro assays, for measuring INMT activity. We further explored the chemical diversity of INMT inhibitors, both natural and synthetic, and highlighted key compounds with therapeutic relevance. Additionally, recent commercial assays for quantifying INMT activity are emphasized. By integrating emerging evidence from structural biology and disease pathology with inhibitor profiling and analytical technologies, this review highlights the underexplored therapeutic potential of targeting INMT and underscores its value as a promising target for drug development and therapeutic applications.
Comparable studies
Other narrative reviews on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neuropharmacology of N,N-dimethyltryptamine | 2016 | Review | |
| N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Humans and animals (general) | 2018 | Review | |
| Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Humans (pharmacokinetics) | 2010 | Review | |
| Pharmahuasca: Human Pharmacology of Oral DMT Plus Harmine Human self-experimenters | 1999 | Review | n = 8 |
| The psychedelic model of schizophrenia: the case of N,N- dimethyltryptamine | 1976 | Review |
Citations in the library
Cites 19
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- Neuropharmacology of N,N-dimethyltryptamine Brain Research Bulletin April 30, 2016
- Enzymatic Formation of Psychotomimetic Metabolites from Normally Occurring Compounds Science August 4, 1961
- N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Frontiers in Neuroscience August 6, 2018
and 14 more in the library