ACS chemical neuroscienceDec 8, 2025

How AET and Its Variants Affect Serotonin Receptors

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 1, 2026

Abstract

All forms of α-Ethyltryptamine (AET) induced a dose-dependent effect on the head-twitch response in mice.

AET, along with its optical isomers (-)-AET and (+)-AET, displayed micromolar affinity for serotonin receptors.
(+)-AET showed weak partial agonist activity in calcium mobilization assays, which was blocked by the serotonin receptor antagonist volinanserin.
The head-twitch response induced by AET was completely blocked by volinanserin, confirming the involvement of serotonin receptors.
Pretreatment with fluoxetine inhibited AET-induced head-twitch response without affecting responses to the classical psychedelic DOI.
The results suggest that AET's effects are mediated through both direct activation of serotonin receptors and increased serotonin release via the serotonin transporter.

Simplified

α-Ethyltryptamine (AET), a synthetic tryptamine formerly used as an antidepressant, has resurfaced as a compound of interest due to its structural and functional overlap with serotonergic psychedelics and entactogens. Here, we characterized the pharmacological properties of racemic AET and its optical isomers,(-)-AET and(+)-AET, focusing on their interactions with the serotonin (or 5-hydroxytryptamine) 5-HTreceptor (5-HTR) and serotonin transporter (SERT). In vitro, all three compounds displaced [H]ketanserin from 5-HTR with micromolar affinity; however, only(+)-AET elicited weak partial agonist activity in calcium mobilization assays, an effect abolished by the 5-HTR antagonist volinanserin. In vivo, all forms of AET induced a dose-dependent effect on the head-twitch response (HTR) in mice, which was completely blocked by volinanserin, confirming the 5-HTR involvement. Notably, pretreatment with fluoxetine abolished AET-induced HTR without affecting responses to the classical psychedelic DOI, implicating SERT-mediated serotonin release in AET's mechanism of action. These findings indicate that AET's behavioral effects rely on a dual mechanism involving both direct 5-HTR activation and indirect serotonergic potentiation via SERT. This dual pharmacology distinguishes AET from classical psychedelics and places it within a unique niche alongside MDMA-like serotonergic agents, highlighting the therapeutic and neuropsychiatric potential of AET isomers for modulating mood and cognition. R S S2A2A2A2A2A2A3

How AET and Its Variants Affect Serotonin Receptors

Abstract

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief