Biological Chemistry
January 2, 2011
Thomas Steinkellner, Michael Freissmuth, Harald H. Sitte et al.
112 citations
Amphetamines like speed, ice, and ecstasy are widely abused for their euphoric and stimulant effects. While animal studies show strong evidence that MDMA causes chronic neurotoxicity, the physiological consequences in humans remain unclear. Differences in metabolism and pharmacokinetics between species and animal strains make it difficult to design realistic human dose paradigms in animal research. This review examines amphetamine toxicity, especially MDMA toxicity, in the context of human disease, setting aside confounding factors such as polydrug use and drug purity.
Neuropharmacology
October 12, 2017
Felix P. Mayer, Nadine V. Burchardt, Ann M. Decker et al.
30 citations
Three isomers of the new psychoactive substance 3-fluorophenmetrazine (2-FPM, 3-FPM, and 4-FPM) inhibit dopamine and norepinephrine transporters with potencies comparable to cocaine (IC50 values below 2.5 μM) but show much weaker effects at the serotonin transporter (IC50 values above 80 μM). They also induce efflux of monoamines via all three transporters, an effect enhanced by the ionophore monensin. These compounds act as monoamine releasers with marked potency at catecholamine transporters implicated in abuse and addiction.
Neuropharmacology
June 23, 2018
Julian Maier, Felix P. Mayer, Dino Luethi et al.
24 citations
4,4′-DMAR, a new psychoactive substance linked to 31 deaths in Europe between June 2013 and February 2014, acts as a potent non-selective monoamine releasing agent. It inhibits dopamine, norepinephrine, and serotonin transporters at low micromolar concentrations (IC50 values below 2 μM) and induces reverse transport via these transporters. It also inhibits the vesicular monoamine transporter 2 in both rat and human cells with potency similar to MDMA. Unlike aminorex and 4-methylaminorex, 4,4′-DMAR strongly affects the serotonin transporter, suggesting fatalities may involve monoaminergic toxicity including serotonin syndrome. Its activity at VMAT2 indicates potential long-term neurotoxicity with chronic abuse.
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.
ACS Chemical Neuroscience
September 30, 2018
Julian Maier, Felix P. Mayer, Simon D. Brandt et al.
15 citations
Aminorex and its analogues are psychostimulants that interact with monoamine transporters, sharing pharmacological similarities with amphetamines and cocaine. Some of these substances, originally failed pharmaceuticals, have reemerged as new psychoactive substances (NPS) for recreational use. Consumption of certain analogues, such as 4-methylaminorex and 4,4'-dimethylaminorex, has been linked to adverse events including death. This review covers the historical background, pharmacodynamic and pharmacokinetic properties, and misuse of these drugs as adulterants. It highlights the dangers of the NPS market, where users often lack knowledge of the pharmacology, potency, or identity of active ingredients.
Frontiers in Psychiatry
January 4, 2023
Felix P. Mayer, Dino Luethi, Lorena B. Areal et al.
1 citation
Psychoactive substances have been consumed throughout human history, first from plants and fungi, then isolated compounds like cocaine, and later synthetic drugs such as LSD. Many recreational drugs also have clinical uses, e.g., amphetamines for ADHD. New psychoactive substances (NPS) have expanded the drug market and improved understanding of structure-activity relationships. Recent clinical trials are reevaluating psychedelics like psilocybin and MDMA for conditions such as depression and PTSD. This special issue includes studies on synthetic opioids, NBOMe derivatives, psilocybin's anxiolytic effects in healthy volunteers, psilocybin reducing body weight in obese rats, and reviews linking mystical experiences to symptom reduction. The collection highlights both risks and therapeutic potential of psychoactive compounds.
ACS Chem Neurosci
March 4, 2026
Nina Kastner, Núria Nadal-Gratacós, Selina Hemmer et al.
correction
A correction notice clarifies that two errors in the original paper do not affect the accuracy of the results, interpretations, or conclusions. The first correction addresses a presentation issue in Table 1, confirming the data are correct. The second correction clarifies that thigmotaxis, a measure of anxiety-like behavior, was evaluated in rats given SDA or SDMA compounds. Compared to saline, only the 10 mg/kg dose of SDA significantly increased thigmotaxis, meaning the rats spent less time in the center of the arena.
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.
Molecular Psychiatry
November 14, 2025
Núria Nadal‐gratacós, Pol Puigseslloses, Laura Hernández‐guzmán et al.
Three novel phenethylamine derivatives—25C-NBF, 25B-NBF, and 25I-NBF—show high affinity and selectivity for the 5-HT2A receptor, with signaling bias toward Gq over β-arrestin pathways similar to serotonin. In mice, they cause moderate head-twitch responses without affecting movement or sensorimotor gating. No rewarding or reinforcing effects were observed, and accumbal dopamine levels in rats remained unchanged. 25C-NBF promotes dendritogenesis, spinogenesis, and increased Bdnf mRNA in vitro and in vivo, reduces despair-like behavior after acute stress, and produces rapid antidepressant effects in a chronic corticosterone model of anhedonia. These findings suggest 25C-NBF may offer a fast-acting antidepressant with no abuse potential or sensorimotor deficits.