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The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator
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The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N -dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na + ) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.
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“Dimethyltryptamine is considered as a natural ligand, an endogenous agonist of the Sig-1R (Fontanilla et al., 2009).”
From The therapeutic potentials of Ayahuasca: possible effects against various diseases of civilization (2016) · cites this paper as Fontanilla et al., 2009
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Metadata
- Authors
- Fontanilla, D., Johannessen, M., Hajipour, A. R., Cozzi, N. V., Jackson, M. B., & Ruoho, A. E.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Ruoho, Arnold E.
- Venue
- Science
- Published
- 2009-02-13
- Volume
- 323
- Issue
- 5916
- Pages
- 934-937
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2947205
- OpenAlex
- W2125368083
- Cited by
- 535
- References
- 30
- Citations by year
- 2026: 27 · 2025: 29 · 2024: 31 · 2023: 26 · 2022: 33 · 2021: 25 · 2020: 37 · 2019: 30 · 2018: 24 · 2017: 38 · 2016: 32 · 2015: 31 · 2014: 34 · 2013: 23 · 2012: 32
- FWCI
- 16.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH065503)
- National Institute on Drug Abuse (F31DA022932)
- National Institute of General Medical Sciences (T32 GM08688, T32GM008688)
- National Institute of Neurological Disorders and Stroke (NS 30016, R01NS030016, R37NS030016)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- N,N-dimethyltryptamine, sigma-1 receptor, hallucinogens, orphan receptors, voltage-gated sodium channels, cardiomyocytes, receptor knockout mice, alkylamine ligands
- MeSH terms
- Sigma-1 Receptor, Animals, Cell Line, Cells, Cultured, Chlorocebus aethiops, N,N-Dimethyltryptamine, Guinea Pigs, Hallucinogens, Ligands, Mice, Inbred C57BL, Myocardium, Tryptamines, Receptors, sigma, Mice, Knockout, COS Cells, Mice, Rats
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