2,5-Dimethoxy-4-hexylamphetamine

2,5-Dimethoxy-4-hexylamphetamine (DOHx or DOHE) is a non-hallucinogenic serotonin receptor modulator of the phenethylamine, amphetamine, and DOx families.^[1][2][3][4]

2,5-Dimethoxy-4-hexylamphetamine

Clinical data
Other names	2,5-Dimethoxy-4-hexylamphetamine; 2,5-Dimethoxy-4-n-hexylamphetamine; 4-Hexyl-2,5-dimethoxyamphetamine; DOHx; DOHX; DOHE
Drug class	Serotonin 5-HT2 receptor modulator; Serotonin receptor antagonist
Identifiers
IUPAC name 1-(4-hexyl-2,5-dimethoxyphenyl)propan-2-amine
PubChem CID	44265170
ChemSpider	23108583
ChEMBL	ChEMBL268890
Chemical and physical data
Formula	C17H29NO2
Molar mass	279.424 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCCCCCC1=CC(=C(C=C1OC)CC(C)N)OC
InChI InChI=1S/C17H29NO2/c1-5-6-7-8-9-14-11-17(20-4)15(10-13(2)18)12-16(14)19-3/h11-13H,5-10,18H2,1-4H3 Key:NICYQFWHLYLNFE-UHFFFAOYSA-N

Pharmacology

DOHx has shown the highest affinity for the serotonin 5-HT_2A and 5-HT_2C receptors of any other assessed DOx drug in multiple studies.^[2][3][5][6] In one study, its affinities for the human serotonin 5-HT₂ receptors were 0.1 nM for the 5-HT_2A receptor, 30 nM for the 5-HT_2B receptor, and 0.7 nM for 5-HT_2C receptor.^[3][4][5] In the case of the serotonin 5-HT_2A receptor, this was 6- to 14-fold higher than DOB, DOI, and DOC and was 9-fold higher than DOPR.^[3][5] In another study, DOHx showed 25-fold higher affinity for the serotonin 5-HT_2A receptor than DOM or DOET, 23- to 28-fold higher affinity than DOPR and DOBU, and 2.8-fold higher affinity than DOAM.^[6] Conversely, it showed only slightly higher or roughly the same affinity for the receptor relative to DOCT (2.5 nM vs. 3.0 nM, respectively).^[6]

In contrast to many other DOx drugs, DOHx, as well as related drugs like DOCT, have been found to act as serotonin 5-HT₂ receptor antagonists rather than as an agonists, and hence would not be expected to be serotonergic psychedelics.^[1][2] In accordance, DOHx, DOCT, and other related drugs do not produce DOM-like effects in rodent drug discrimination tests.^[2] DOHx has also been assessed and found to act as a silent antagonist of the serotonin 5-HT_2B receptor (E_maxTooltip maximal efficacy = 0%).^[7]

Chemistry

DOHx is part of the series of 4-alkylated DOx drugs that includes DOM (methyl), DOET (ethyl), DOPR (propyl), DOBU (butyl), and DOAM (amyl/pentyl), with DOHx having a hexyl substitution and hence the longest alkyl chain of the preceding drugs.^[1][3][4] Following DOHx in the series are DOHP (heptyl) and then DOCT (octyl).^[2][6]

History

DOHx was first described in the scientific literature by at least 1989.^[8]