Tryptamine and dimethyltryptamine inhibit indoleamine 2,3 dioxygenase and increase the tumor-reactive effect of peripheral blood mononuclear cells.
Melissa Cavalheiro Tourino, Edson Mendes De Oliveira, Luziane Potrich Bellé, Franciele Hinterholz Knebel, Renata Chaves Albuquerque, Felipe Augusto Dörr, Sabrina Sayori Okada, Silene Migliorini, Irene Silva Soares, Ana Čampa
Cell biochemistry and function July 2013 DOI: 10.1002/cbf.2980 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Recombinant human IDO enzyme, A172 human glioma cells, and human peripheral blood mononuclear cells |
| Interventions | Tryptamine N N-dimethyltryptamine (DMT) |
| Topics | 5-MeO-DMT DMT |
| Keywords | Immune escape Kynurenine pathway Tolerance Tryptophan metabolism Tumor growth |
| Key findings | Tryptamine and DMT inhibited recombinant human IDO as non-competitive inhibitors (Ki 156 and 506 μM), an effect also seen on IDO in A172 glioma cells; both increased peripheral blood mononuclear cell cytotoxic activity in co-culture, which the authors conclude contributed to a more effective tumor-reactive response. |
Abstract
Indoleamine 2,3-dioxygenase (IDO) is an interferon-γ (IFN-γ)-induced tryptophan-degrading enzyme, producing kynurenine (KYN) that participates in the mechanism of tumor immune tolerance. Thus, IDO inhibition has been considered a strategy for anticancer therapy. The aim of this study was to identify whether the metabolites originated from the competitive routes of tryptophan metabolism, such as the serotonergic or N, N-dimethyltryptamine (DMT) pathways, have inhibitory effects on recombinant human IDO (rhIDO) activity. Serotonin and melatonin had no effect; on the other hand, tryptamine (TRY) and DMT modulated the activity of rhIDO as classical non-competitive inhibitors, with Ki values of 156 and 506 μM, respectively. This inhibitory effect was also observed on constitutively expressed or IFN-γ-induced IDO in the A172 human glioma cell line. TRY and DMT increased the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays. We conclude that the IDO inhibition by TRY and DMT contributed to a more effective tumor-reactive response by the PBMCs.
Comparable studies
Other preclinical and animal studies on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Mice and cell lines | 2009 | Experimental study | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitor Rats | 1971 | Experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study |
Citations in the library
Cited by 18
- Neuropharmacology of N,N-dimethyltryptamine Brain Research Bulletin April 30, 2016
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Frontiers in Neuroscience August 6, 2018
- Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities Frontiers in Immunology July 14, 2015
- The clinical pharmacology and potential therapeutic applications of 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT) Journal of Neurochemistry February 12, 2022
and 13 more in the library
Cites 4
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter. Journal of Neural Transmission September 12, 2009
- When the Endogenous Hallucinogenic Trace AmineN,N-Dimethyltryptamine Meets the Sigma-1 Receptor Science Signaling March 10, 2009
- In vivo long-term kinetics of radiolabeled n,n-dimethyltryptamine and tryptamine. Journal of Nuclear Medicine June 2011