5-Chloro-αET

5-Chloro-αET (code name PAL-526), or 5-chloro-AET, also known as 5-chloro-α-ethyltryptamine, is a serotonergic agent of the tryptamine and α-alkyltryptamine families.^[1] It is the derivative of α-ethyltryptamine (αET or AET) with a 5-chloro substitution.^[1]

Other names5-Chloro-AET; 5-Chloro-α-ethyltryptamine; PAL-526; PAL526

Drug classSerotonin releasing agent; Serotonin 5-HT_2A receptor agonist

PubChem CID

112485369

ChemSpider

26493372

Quick facts Clinical data, Other names ...

5-Chloro-αET
Clinical data


Other names	5-Chloro-AET; 5-Chloro-α-ethyltryptamine; PAL-526; PAL526
Drug class	Serotonin releasing agent; Serotonin 5-HT_2A receptor agonist
Identifiers
IUPAC name 1-(5-chloro-1H-indol-3-yl)butan-2-amine
PubChem CID	112485369
ChemSpider	26493372
ChEMBL	ChEMBL3330647
Chemical and physical data
Formula	C₁₂H₁₅ClN₂
Molar mass	222.72 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CCC(CC1=CNC2=C1C=C(C=C2)Cl)N
InChI InChI=1S/C12H15ClN2/c1-2-10(14)5-8-7-15-12-4-3-9(13)6-11(8)12/h3-4,6-7,10,15H,2,5,14H2,1H3 Key:LBURKXNSAFJELW-UHFFFAOYSA-N

Pharmacology

Pharmacodynamics

The drug is known to act as a potent serotonin releasing agent (SRA) and relatively weak serotonin 5-HT_2A receptor near-full agonist.^[1] It shows negligible induction of norepinephrine and dopamine release but does act as a very weak dopamine reuptake inhibitor (DRI).^[1] 5-Chloro-αET's EC₅₀Tooltip half-maximal effective concentration and IC₅₀Tooltip half-maximal inhibitory concentration values are 33.2 nM for serotonin release, 249 nM (E_maxTooltip maximal efficacy = 87%) for serotonin 5-HT_2A receptor agonism (7.5-fold lower than for serotonin release), 1,838 nM for dopamine reuptake inhibition (55-fold lower than for serotonin release), and >10,000 nM for norepinephrine release.^[1] The monoamine release assays were performed in rat brain synaptosomes.^[1]

Several close analogues of 5-chloro-αET, including 5-chloro-αMT and 5-fluoro-αMT, are known to be potent monoamine oxidase inhibitors (MAOIs), specifically of monoamine oxidase A (MAO-A).^[2]

Chemistry

Analogues

Analogues of 5-chloro-αET include α-ethyltryptamine (AET), 5-fluoro-αET, 5-chloro-αMT, and 5-fluoro-αMT, among others.^[1]

History

5-Chloro-AET was first described in the scientific literature by at least 1963.^[3]^[4]

Society and culture

Legal status

Canada

5-Chloro-AET is not an explicitly nor implicitly controlled substance in Canada as of 2025.^[5]

United States

5-Chloro-AET is not an explicitly controlled substance in the United States.^[6] However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

References

[1]
Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorg Med Chem Lett. 24 (19): 4754–4758. doi:10.1016/j.bmcl.2014.07.062. PMC 4211607. PMID 25193229. The racemic a-alkyl tryptamines 7a, 7b, 7c, 7d, 7e, and 7f were synthesized by nitro olefin formation followed by lithium ammonium hydride reduction (Scheme 2).32 [...] a-Ethylation of the 5-chloro and 5-fluoro substituted tryptamines, to form 7e and 7f respectively, also weakened NE release activity compared to their a-methyl analogs, but 7e flipped to become a weak DA uptake inhibitor. [...] In the a-ethyltryptamine series, the 5-chloro analog (7e) and 5-fluoro analog (7f) both weakened substantially as 5-HT2A agonists compared to their a-methyl- and non-alkylated tryptamine analogs (7b/7c and 4h/4j), with EC50 values of 249 nM and 246 nM, respectively. [...] Table 1 Comparison of the DAT, SERT, and NET-mediated release activity and 5-HT2A receptor activity of substituted tryptamines [...] ^d Value is IC50 for uptake inhibition in nM.
[2]
Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK (2019). "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Front Pharmacol. 10 1590. doi:10.3389/fphar.2019.01590. PMC 6989591. PMID 32038257. Several close analogues of 5-chloro-αET, such as 5-chloro-αMT and 5-fluoro-αMT, are known to be potent monoamine oxidase inhibitors (MAOIs).
[3]
Brimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. OL 4850660M. [...] 5-chloro-, but not 6-chloro-, derivatives of α-methyl- and α-ethyl-tryptamine produced behavioural changes in animals (Whittle and Young, 1963); [...]
[4]
Whittle BA, Young EH (July 1963). "The Synthesis and Pharmacological Activity of Some Chloro-α-alkyltryptamines". J Med Chem. 6 (4): 378–380. doi:10.1021/jm00340a009. PMID 14184890. The synthesis of eight new monochloro analogs of a-methyl- and a-ethyltryptamines are described. These compounds were prepared by condensations of 4-, 5-, 6-, and 7-chloroindole-3-aldehydes with either nitroethane or nitropropane and subsequent reduction of the condensation products with lithium aluminum hydride. The tryptamines have been found to possess stimulant and anticonvulsant properties in rodents and to produce behavioral changes in cats. [...]
[5]
"Controlled Drugs and Substances Act". Department of Justice Canada. 5 December 2025. Retrieved 20 January 2026.
[6]
Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026) (PDF), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026