Molecular Psychiatry
March 14, 2024
Pol Puigseslloses, Gabriel Ketsela, Nicola Weiss et al.
23 citations
All tested 5-MeO-tryptamines selectively bind to 5-HT1A receptors over 5-HT2A receptors, with computational docking predicting better interaction in the 5-HT1A binding pocket. These compounds also interact with the serotonin transporter (SERT), where molecular size of the amino group influences affinity. 5-MeO-pyr-T acts as the most potent partial 5-HT releaser. All tryptamines elicit the head twitch response in mice, indicating potential hallucinogenic effects primarily mediated by 5-HT2A receptors, but 5-HT1A activation attenuates this response. Tryptamines producing stronger hypothermic responses via 5-HT1A tend to show lower hallucinogenic effects, highlighting opposing roles of the two receptors. Some compounds with low hallucinogenic effects remain potent 5-HT2A agonists, offering insight into non-hallucinogenic therapeutic ligands.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
March 1, 2022
Deborah Rudin, John D McCorvy, Grant C Glatfelter et al.
18 citations
Derivatives of (2-aminopropyl)indole and (2-aminopropyl)benzofuran are new psychoactive substances with stimulant effects. This study characterized six isomers of the sulfur-based analog (2-aminopropyl)benzo[β]thiophene (APBT) in vitro and three isomers in vivo. APBTs inhibited monoamine reuptake and induced transporter-mediated substrate release, similar to MDMA, but did not stimulate locomotion in mice. Instead, they acted as full agonists at 5-HT2 receptor subtypes and induced head-twitch responses, indicating psychedelic-like activity. Replacing oxygen with sulfur enhanced serotonin transporter release potency and 5-HT2 receptor activity, shifting the profile toward psychedelic and entactogenic effects with minimal psychomotor stimulation, suggesting potential for drug-assisted psychotherapy.
International journal of molecular sciences
November 30, 2021
Thomas J F Angenoorth, Stevan Stankovic, Marco Niello et al.
18 citations
Many psychoactive compounds primarily interact with high-affinity monoamine transporters, but their interactions with low-affinity, high-capacity transporters like human organic cation transporters (hOCTs) and the plasma membrane monoamine transporter (hPMAT) are understudied. Using radiotracer-based uptake inhibition assays in HEK293 cells, 17 psychoactive substances were tested. Most compounds inhibited hOCT1 and hOCT2 in the low micromolar range, while few affected hOCT3 or hPMAT. Methylphenidate and ketamine selectively inhibited hOCT1 or hOCT2, respectively, and MDMA potently inhibited hOCT1, hOCT2, and hPMAT. Enantiospecific differences were observed for R- and S-α-PVP and R- and S-citalopram. These findings highlight the importance of studying drug interactions with hOCTs and hPMAT for regulating monoamine concentrations and xenobiotic clearance.
ACS Chemical Neuroscience
December 2, 2025
Nina Kastner, Núria Nadal‐gratacós, Selina Hemmer et al.
Replacing the 1,3-benzodioxole group in MDMA (ecstasy) with a 1,3-benzoxathiole yields two analogues, SDA and SDMA, that interact with monoamine transporters similarly to MDMA but with key differences. SDA and SDMA inhibit dopamine and norepinephrine transporters more potently than MDMA and act as partial releasers at serotonin and dopamine transporters. Metabolism studies show SDA and SDMA are cleared faster, while MDMA and MDA degrade only weakly. In mice, SDMA does not produce rewarding effects, unlike MDMA, and SDA only shows a preference for the drug-paired compartment at the lowest dose. SDMA shares similar locomotor and hyperthermic profiles with MDMA, whereas SDA induces increased hyperlocomotion and more sustained hyperthermia. SDMA may be a safer candidate for further study.