Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/118695
Title: Cardiac effects of two hallucinogenic natural products, N,N-dimethyl-tryptamine and 5-methoxy-N,N-dimethyl-tryptamine
Author(s): Neumann, JoachimLook up in the Integrated Authority File of the German National Library
Dietrich, Tobias
Azatsian, Karyna
Hofmann, BrittLook up in the Integrated Authority File of the German National Library
Gergs, UlrichLook up in the Integrated Authority File of the German National Library
Issue Date: 2025
Type: Article
Language: English
Abstract: It is unclear whether hallucinogenic tryptamine derivatives namely N,N-dimethyl-tryptamine (DMT) and 5-methoxy-N,N-dimethyl-tryptamine (5-MeO-DMT) exert positive inotropic effects in the human heart. Therefore, we measured the inotropic effects of these drugs in isolated left and right atrial preparations of mice that overexpress human 5-HT4 receptors (5-HT4-TG) and preparations from wild type mice (WT). Moreover, we measured force of contraction in isolated right atrial preparations from adult patients, obtained in the process of open heart surgery due to severe coronary heart disease. DMT and 5-MeO-DMT augmented the force of contraction in isolated paced (1 Hz) left atrial preparations from 5-HT4-TG and raised the spontaneous beating rate of right atrial preparations from 5-HT4-TG. The drugs elevated force of contraction in paced (1 Hz) human right atrial muscle preparations. The maximum inotropic effects of DMT and 5-MeO-DMT were smaller at 10 µM (about 65%) than that of 1 µM 5-HT on the left atria from 5-HT4-TG. The maximum increase in the beating rate due to DMT and 5-MeO-DMT amounted 40 ± 5% of the effect of 5-HT on right atrial preparations from 5-HT4-TG (n = 5–6). DMT and 5-MeO-DMT were inactive in WT. The potency of 5-MeO-DMT to increase force of contraction could be increased by pre-treatment of human atrial preparations by the phosphodiesterase inhibitor cilostamide (1 µM). 5-MeO-DMT increased the phosphorylation state of phospholamban at serine 16 in isolated left atrial muscle strips of 5-HT4-TG. In summary, DMT and 5-MeO-DMT acted as partial agonists on human 5-HT4 receptors.
URI: https://opendata.uni-halle.de//handle/1981185920/120653
http://dx.doi.org/10.25673/118695
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Journal Title: Scientific reports
Publisher: Springer Nature
Publisher Place: [London]
Volume: 15
Original Publication: 10.1038/s41598-025-91400-6
Appears in Collections:Open Access Publikationen der MLU

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