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

Pharmacology Pharmacodynamics DOHx has shown the highest affinity for the serotonin 5-HT2A and 5-HT2C receptors of any other assessed DOx drug in multiple studies. In one study, its affinities for the human serotonin 5-HT2 receptors were 0.1nM for the 5-HT2A receptor, 30nM for the 5-HT2B receptor, and 0.7nM for 5-HT2C receptor. In the case of the serotonin 5-HT2A receptor, this was 6- to 14-fold higher than DOB, DOI, and DOC and was 9-fold higher than DOPR. In another study, DOHx showed 25-fold higher affinity for the serotonin 5-HT2A receptor than DOM or DOET, 23- to 28-fold higher affinity than DOPR and DOBU, and 2.8-fold higher affinity than DOAM. Conversely, it showed only slightly higher or roughly the same affinity for the receptor relative to DOCT (2.5nM vs. 3.0nM, respectively).

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. In accordance, DOHx, DOCT, and other related drugs do not produce DOM-like effects in rodent drug discrimination tests. DOHx has also been assessed and found to act as a silent antagonist of the serotonin 5-HT2B receptor ( = 0%).

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. Following DOHx in the series are DOHP (heptyl) and then DOCT (octyl).

Synthesis The chemical synthesis of DOHx has been described. "The work was started towards two additional compounds but these never got past the first “ketone and phenol” stage. p-Dimethoxybenzene was brought into reaction with n-caproic acid with polyphosphoric acid (aiming towards 2,5-dimethoxy-4-n-hexylamphetamine, DOHE) but this was dropped when DOAM proved to be down in potency. And the reaction between p-dimethoxybenzene and benzoyl chloride with anh. aluminum chloride went well (aiming towards 2,5-dimethoxy-4-benzylamphetamine, DOBZ). A goodly amount of the phenol (2-hydroxy-5-methoxybenzophenone) was obtained as fine yellow crystals, but this line of inquiry was also dropped."

History DOHx was first described in the scientific literature by Richard Glennon and colleagues by 1989.

Society and culture Legal status Canada DOHx is a controlled substance in Canada under phenethylamine blanket-ban language.

See also DOx (psychedelics)

References

External links DOHE - Isomer Design