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2,4,5-Trimethoxyphenethylamine
Pharmaceutical compound From Wikipedia, the free encyclopedia
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2C-O, also known as 2,4,5-trimethoxyphenethylamine (2,4,5-TMPEA) or TMPEA-2, is a serotonin receptor modulator of the phenethylamine and 2C families related to the psychedelic drug mescaline.[1][3][2][4] It is a positional isomer of mescaline (3,4,5-trimethoxyphenethylamine)[1][3][5] and is the α-desmethyl analogue of 2,4,5-trimethoxyamphetamine (TMA-2).[1][3][5] The drug is the parent compound of the 2C-O series of drugs.[6] 2C-O appears to be inactive in terms of psychoactive effects in humans, at least at doses that have been assessed.[1][3][7][6][8] 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.[4] 2C-O was first described by Max Jansen in 1931 and was further described by Alexander Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[1][3][2]
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Use and effects
Summarize
Perspective
2C-O at a dose of under 300 mg by injection was reported to produce similar psychedelic effects as mescaline by Max Jansen in 1931, albeit with more nausea and no euphoria.[1][2] Conversely, in a subsequent report described by Alexander Shulgin, it was said to be indistinguishable from placebo at a dose of up to 300 mg orally.[1][3][7][6][9] The drug was also combined with the monoamine oxidase inhibitor (MAOI) harmaline, which acts as a reversible inhibitor of monoamine oxidase A (RIMA).[10] Even with a dose of 150 mg harmaline and 200 mg 2C-O orally however, there were no additional hallucinogenic effects that could not be explained by harmaline alone.[10]
According to Shulgin, the present-day consensus is that 2C-O by itself is inactive.[1][7][6][8] In PiHKAL (Phenethylamines I Have Known and Loved), its dose is listed as greater than 300 mg orally and its duration as unknown.[1] Although 2C-O does not seem to produce effects by itself, the drug at a dose of 200 mg orally was reported to strongly potentiate the action of 100 mg mescaline when employed as pretreatment 45 minutes prior to the administration of mescaline.[1][9]
The apparent inactivity of 2C-O (2,4,5-trimethoxyphenethylamine) in humans has been described as enigmatic for several reasons.[5] This is because other 2C drugs are active, because 2C-O's amphetamine (α-methyl) counterpart 2,4,5-trimethoxyamphetamine (TMA-2) is active, and because the drug's positional isomer mescaline (3,4,5-trimethoxyphenethylamine) is active.[5][1]
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Interactions
Pharmacology
Summarize
Perspective
2C-O has been found to act as full agonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors.[4] However, it showed more than two orders of magnitude lower potency in activating the serotonin 5-HT2A receptor than 2C-B and 2C-I.[4] On the other hand, 2C-O was similar in potency to mescaline as a serotonin 5-HT2A receptor agonist, with EC50 values of 195 nM and 646 nM in terms of Gq signaling, respectively.[4] The drug also showed higher efficacy than mescaline as a serotonin 5-HT2A receptor agonist (Emax = 96–100% vs. 33–74%, respectively).[4]
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.[7][6] However, an in-vitro study using rabbit liver tissue found that 2C-O was deaminated 25% alone and 25% with the monoamine oxidase inhibitor (MAOI) semicarbazide after 1 hour whereas mescaline was deaminated 60% alone and 0% with semicarbazide after 1 hour.[11] These findings suggest that 2C-O may be less susceptible to metabolism by monoamine oxidase (MAO) than mescaline.[11] Moreover, it is now known that 2C-O shows far lower potency as a serotonin 5-HT2A receptor agonist than other 2C drugs.[4]
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 (α-methyl) analogue TMA-2, as well as derivatives like MEM, are potent psychedelics.[6][1][8]
Chemistry
2C-O, also known as 2,4,5-trimethoxyphenethylamine (2,4,5-TMPEA), is a substituted phenethylamine and 2C derivative.[1]
Synthesis
The chemical synthesis of 2C-O has been described.[1][3]
Analogues
Notable positional isomers of 2C-O (2,4,5-TMPEA) include mescaline (3,4,5-TMPEA) and Ψ-2C-O (2,4,6-TMPEA).[1]
Derivatives
A variety of derivatives of 2C-O, named 2C-O-2 (4-ethoxy-2,5-dimethoxyphenethylamine) through 2C-O-27, have been developed and studied.[6] One notable derivative is 2C-O-4 (4-isopropoxy-2,5-dimethoxyphenethylamine).[6]
25O-NBOMe is the N-(2-methoxybenzyl)- (NBOMe) derivative of 2C-O.[4] It is far more potent as a serotonin 5-HT2 receptor agonist than 2C-O.[4]
The tetramethoxyphenethylamines TeMPEA-1 (2,3,4,5-TeMPEA) and TeMPEA-3 (2,3,5,6-TeMPEA) as well as pentamethoxyphenethylamine (PeMPEA) are derivatives of 2C-O.[1][3]
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History
2C-O was first described by Max Jansen in 1931 and was reported by him to produce psychedelic effects similar to those of mescaline.[12][2] However, subsequent tests in the 1960s and 1970s, for instance by A. Dittrich and Alexander Shulgin, suggested that 2C-O is actually inactive as a psychedelic in animals and humans.[12][1][3][9]
Society and culture
Legal status
Canada
As of October 31, 2016, 2C-O is a controlled substance (Schedule III) in Canada.[13]
United States
2C-O is a Schedule I substance, as a positional isomer of mescaline.
United Kingdom
2C-O and all other compounds featured in PiHKAL are Class A drugs in the United Kingdom.
See also
References
External links
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