Cited by 557Pharmacological Receptor Mechanisms and EffectsPsychedelics and Drug StudiesReceptor Mechanisms and Signaling

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The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator

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Fontanilla, Dominique, Johannessen, Molly, Hajipour, Abdol R., Cozzi, Nicholas V., Jackson, Meyer B., Ruoho, Arnold E.·2009·Science

DOI 10.1126/science.1166127PMC PMC2947205

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Abstract

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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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.
ORCID: Hajipour, Abdol R.
Cozzi, Nicholas V.
Jackson, Meyer B.
Ruoho, Arnold E.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2009-02-13
Volume: 323
Issue: 5916
Pages: 934-937
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1166127
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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The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator

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