Ariadne

Clinical data
Trade names	Dimoxamine (tentative)
Other names	ARIADNE; 4-Methyl-2,5-dimethoxy-α-ethylphenethylamine; 2,5-Dimethoxy-4-methyl-α-ethylphenethylamine; 4C-D; 4C-DOM; "Four-carbon DOM"; α-Et-2C-D; α-Ethyl-2C-D; BL-3912; BL3912; Dimoxamine
Drug class	Serotonin5-HT2A,5-HT2B, and5-HT2C receptoragonist; Non-hallucinogenicserotonin5-HT2A receptoragonist
Legal status
Legal status	?
Identifiers
IUPAC name 1-(2,5-dimethoxy-4-methylphenyl)butan-2-amine
CAS Number	52842-58-7 52842-59-8 ((R)-isomer)
PubChemCID	169886
ChemSpider	148565 Y
UNII	09426ZTO78
CompTox Dashboard(EPA)	DTXSID501343240 DTXSID30967314, DTXSID501343240
Chemical and physical data
Formula	C13H21NO2
Molar mass	223.316 g·mol−1
3D model (JSmol)	Interactive image
SMILES O(c1cc(c(OC)cc1C[C@H](N)CC)C)C
InChI InChI=1S/C13H21NO2/c1-5-11(14)7-10-8-12(15-3)9(2)6-13(10)16-4/h6,8,11H,5,7,14H2,1-4H3 Y Key:MLYCFWZIAJAIGW-UHFFFAOYSA-N Y
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Ariadne, also known chemically as4C-D or4C-DOM, by its developmental code nameBL-3912, and by its former tentative brand nameDimoxamine, is a little-knownpsychoactive drug of thephenethylamine,amphetamine, andphenylisobutylamine families.^[1][2][3][4] It is ahomologue of thepsychedelics2C-D andDOM.^[1][2][3][4]

The drug is aserotonin receptoragonist, including of the serotonin5-HT_2A receptor.^[1] However, it is non-hallucinogenic in animals and humans, although it still has somepsychoactive effects.^[1][2][3] It may be non-hallucinogenic due to lower-efficacypartial agonism of the serotonin 5-HT_2A receptor.^[1]

Ariadne was developed byAlexander Shulgin.^[1][2] It was studied atBristol Laboratories as anantidepressant and for various other uses but was never marketed.^[1][4][3] There has been renewed interest in Ariadne in the 2020s owing to increased interest in psychedelics for treatment ofpsychiatric disorders.^[1]

In his 1991 bookPiHKAL,Alexander Shulgin reported testing Ariadne on himself up to a dose of 32 mg, finding that it produced "the alert of a psychedelic, with none of the rest of the package".^[2] Very little published data exists about the human pharmacology of Ariadne apart from Shulgin's limited testing; unpublished human trials reportedly observed somepsychoactive effects, but nohallucinations.^[5][1]

In his 2011 bookThe Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds, Shulgin described (R)-Ariadne as increasingmental alertness and producing feelings ofwell-being at doses of 25 to 50 mg.^[3] It was claimed to improve symptoms ofmanic depression inpsychotic individuals at doses of 50 to 100 mg and to improve symptoms ofParkinson's disease at a dosage of 100 mg/day.^[3][1] Doses of up to 300 mg resulted in analtered state of consciousness but still no psychedelic effects.^[1][3] For comparison, DOM shows psychoactive sub-hallucinogenic effects at doses of 1 to 3 mg and psychedelic effects at doses of more than 3 mg.^[1]

Ariadne is apotent andselectiveagonist of theserotonin5-HT₂ receptors, including of the serotonin5-HT_2A,5-HT_2B, and5-HT_2C receptors.^[1] However, it is lessefficacious in activating the serotonin 5-HT_2A receptor, including theG_q, G₁₁, andβ-arrestin2 signaling pathways, compared to the related drugDOM, and this weakerpartial agonism may be responsible for its lack of psychedelic effects.^[1] In addition to the serotonin 5-HT₂ receptors, Ariadne is a lower-affinity agonist of the serotonin5-HT₁ receptors.^[1] Ariadne shows essentially no activity at themonoamine transporters.^[1]

Ariadne shows a markedly attenuatedhead-twitch response, a behavioral proxy of psychedelic effects, in animals.^[1] It is thought that the reduced efficacy of Ariadne in activating the serotonin 5-HT_2A receptor is responsible for its non-hallucinogenic nature.^[1] Ariadne was also shown to produce stimulus generalization in rats trained to respond toMDMA^[6] orLSD.^[5] In monkeys, the drug was found to possiblyincrease motivation, as it caused monkeys that had stopped running mazes to begin running them again.^[2] Ariadne has also been found to be effective in ananimal model ofParkinson's disease, where it reversedmotor deficits similarly tolevodopa.^[1]

Serotonin 5-HT_2A receptor agonists have been found to increasedopamine levels in thenucleus accumbens and othermesolimbic areas and non-hallucinogenic serotonin 5-HT_2A receptor agonists like Ariadne may do so without producing psychedelic effects.^[1] This action may underlie the preliminary observations of effectiveness of Ariadne in the treatment ofparkinsonism in animals and humans.^[1]

Ariadne, also known as 4-methyl-2,5-dimethoxy-α-ethylphenethylamine, is asubstituted phenethylamine andamphetaminederivative.^[2][3] It is theanalogue of2,5-dimethoxy-4-methylamphetamine (DOM) in which theα-methylgroup has been replaced with an α-ethyl group and is the analogue of2,5-dimethoxy-4-methylphenethylamine (2C-D) with an ethyl group substituted at the α carbon.^[1][2][3]

Ariadne's alternative name4C-DOM or4C-D stands for "four-carbon DOM", whereas the name of 2C-D stands for "two-carbon DOM".^[1] Another name of Ariadne isα-Et-2C-D, which stands for α-ethyl-2C-D.^[7]Racemic Ariadne is additionally known by the former developmental code nameBL-3912, while the (R)-enantiomer of Ariadne is known by the former developmental code nameBL-3912A.^[1][3]

Other related compounds include4C-B (the α-ethyl homologue of2C-B andDOB) and4C-T-2 (the α-ethyl homologue of2C-T-2 andAleph-2).^[2]

Ariadne was first synthesized byAlexander Shulgin.^[1][2] Shulgin reported that the drug was tested byBristol Laboratories as anantidepressant, in an anecdote where he was explaining how human testing is invaluable (compared to animal testing) on drugs that change the state of the mind. He said, "Before they launched into a full multi-clinic study to determine whether it's going to be worth the animal studies or not, every person on the board of directors took it."^[4] InThe Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds (2011), he described it also being evaluated for increasingmental alertness ingeriatric individuals, treatingParkinson's disease, and treatingpsychosis andmanic depression.^[3][1] The tentative commercial name of Ariadne wasDimoxamine.^[3] (R)-Ariadne was said to have completedphase 2clinical trials, but the actual clinical data were never disclosed and further development was halted due to strategic economic reasons.^[1]

• BMB-201
• DOET
• ITI-1549
• Zalsupindole

• ARIADNE Entry atPiHKAL·info

• 5-HT2B agonists
• 5-HT2C agonists
• 2,5-Dimethoxyphenethylamines
• Abandoned drugs
• Experimental non-hallucinogens
• Non-hallucinogenic 5-HT2A receptor agonists
• Phenylisobutylamines
• Pro-motivational agents

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