2,4,5-Trimethoxyphenethylamine
2C-O, also known as 2,4,5-trimethoxyphenethylamine or TMPEA-2, is a serotonin receptor modulator of the phenethylamine and 2C families related to the psychedelic drug mescaline. It is a positional isomer of mescaline and is the α-desmethyl analogue of 2,4,5-trimethoxyamphetamine. The drug is the parent compound of the 2C-O series of drugs. 2C-O appears to be inactive in terms of psychoactive effects in humans, at least at doses that have been assessed. In any case, it is a low-potency full agonist of the serotonin 5-HT2 receptors in vitro, including of the serotonin 5-HT2A receptor. 2C-O was first described by Max Jansen in 1931 and was further described by Alexander Shulgin in his 1991 book PiHKAL.
Use and effects
2C-O at a dose of under 300mg by injection was reported to produce similar psychedelic effects as mescaline by Max Jansen in 1931, albeit with more nausea and no euphoria. Conversely, in a subsequent report described by Alexander Shulgin, it was said to be indistinguishable from placebo at a dose of up to 300mg orally. The drug was also combined with the monoamine oxidase inhibitor harmaline, which acts as a reversible inhibitor of monoamine oxidase A. Even with a dose of 150mg harmaline and 200mg 2C-O orally however, there were no additional hallucinogenic effects that could not be explained by harmaline alone.According to Shulgin, the present-day consensus is that 2C-O by itself is inactive. In PiHKAL, its dose is listed as greater than 300mg orally and its duration as unknown. Although 2C-O does not seem to produce effects by itself, the drug at a dose of 200mg orally was reported to strongly potentiate the action of 100mg mescaline when employed as pretreatment 45minutes prior to the administration of mescaline.
The apparent inactivity of 2C-O in humans has been described as enigmatic for several reasons. This is because other 2C drugs are active, because 2C-O's amphetamine counterpart 2,4,5-trimethoxyamphetamine is active, and because the drug's positional isomer mescaline is active.
Pharmacology
2C-O has been found to act as full agonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. However, it showed more than two orders of magnitude lower potency in activating the serotonin 5-HT2A receptor than 2C-B and 2C-I. On the other hand, 2C-O was similar in potency to mescaline as a serotonin 5-HT2A receptor agonist, with values of 195nM and 646nM in terms of Gq signaling, respectively. The drug also showed higher efficacy than mescaline as a serotonin 5-HT2A receptor agonist.It has been said in the past that it is unclear whether the apparent inactivity of 2C-O is due to strong metabolism or low affinity and/or efficacy at the serotonin 5-HT2A receptor. However, an in-vitro study using rabbit liver tissue found that 2C-O was deaminated 25% alone and 25% with the monoamine oxidase inhibitor semicarbazide after 1hour whereas mescaline was deaminated 60% alone and 0% with semicarbazide after 1hour. These findings suggest that 2C-O may be less susceptible to metabolism by monoamine oxidase than mescaline. Moreover, it is now known that 2C-O shows far lower potency as a serotonin 5-HT2A receptor agonist than other 2C drugs.
Although 2C-O and certain derivatives such as 2C-O-4 appear to be inactive or of low potency in humans, 2C-O derivatives show potent serotonin 5-HT2A receptor agonism in vitro, and the amphetamine analogue TMA-2, as well as derivatives like MEM, are potent psychedelics.
Chemistry
2C-O, also known as 2,4,5-trimethoxyphenethylamine, is a substituted phenethylamine and 2C derivative.Synthesis
The chemical synthesis of 2C-O has been described.Analogues
Notable positional isomers of 2C-O include mescaline and Ψ-2C-O.Derivatives
A variety of derivatives of 2C-O, named 2C-O-2 through 2C-O-27, have been developed and studied. A couple of notable derivatives are 2C-O-4 and 2C-O-22.25O-NBOMe is the N-(2-methoxybenzyl)- derivative of 2C-O. It is far more potent as a serotonin 5-HT2 receptor agonist than 2C-O.
The tetramethoxyphenethylamines TeMPEA-1 and TeMPEA-3 as well as pentamethoxyphenethylamine are derivatives of 2C-O.