2C-T-33, also known as 4-(3-methoxybenzylthio)-2,5-dimethoxyphenethylamine, is a serotonin receptor agonist of the phenethylamine and 2C families. It was first synthesized and described by Daniel Trachsel in 2003. The drug is not known to have ever been tested in humans and its active human doses have not been reported.
Pharmacology.
2C-T-33 shows high affinity for the serotonin 5-HT2A receptor (Ki = 1.7nM) and to a much lesser extent for the serotonin 5-HT2C receptor (Ki = 75nM; 44-fold lower than for 5-HT2A). In terms of serotonin 5-HT2A receptor activation, its is 26nM and its is 40%. Hence, 2C-T-33 acts as a low-efficacy partial agonist of the serotonin 5-HT2A receptor. The drug shows higher affinity for the serotonin 5-HT2A receptor but much lower potency and efficacy in activating the receptor compared to 2C-T or 2C-B (which had values of Ki = 6.9–49nM, = 2.0–2.1nM, and = 75–92%). In contrast to most other 2C drugs and serotonergic psychedelics, 2C-T-33 appears to be completely inactive as an agonist of the serotonin 5-HT2B receptor ( > 10,000nM). The drug has also been assessed at a number of other targets.
The drug did not significantly produce the head-twitch response (HTR), a behavioral proxy of psychedelic effects, in rodents, and hence may not have hallucinogenic effects in humans. Its analogue 2C-T-27 (which lacks the methoxy group on the added benzyl ring) significantly and potently induces the HTR in rodents. However, the HTR induced by 2C-T-27 is far weaker in magnitude than that induced by other 2C-T-X drugs and other serotonergic psychedelics. For example, 2C-T (or 2C-T-1) induced about 7-fold more HTR events than 2C-T-33. In contrast to the lack of assessment of 2C-T-33 in humans, 2C-T-27 has been evaluated and found to be active as a psychedelic in humans with a dose range of 80 to 130mg.
The lack of HTR with 2C-T-33 may be due to its low-efficacy partial agonism of the serotonin 5-HT2A receptor and the receptor not being activated strongly enoughly. The potencies of psychedelics in inducing the HTR are positively correlated with their efficacies in activating the serotonin 5-HT2A receptor. The bulky 4 substitution of 2C-T-33 may be too large to accommodate the binding pocket of the serotonin 5-HT2A receptor in terms of maintaining robust receptor activation. Similar findings have been observed for other phenethylamines with bulky 4-position substitutions, such as DOHx, DOBz, and 4-PhPr-3,5-DMA.
In addition to its potential psychoactive effects, 2C-T-33 has shown anti-inflammatory effects in animal studies similarly to other serotonin 5-HT2A receptor agonists and serotonergic psychedelics. However, 2C-T-33 was the least effective assessed phenethylamine and was far less effective than other phenethylamines such as 2C-I, DOIB, 2C-B, ("R")-DOI, and 2,5-DMA, among others.