2,5-Dimethoxyamphetamine

Pharmacodynamics

2,5-DMA is a low-potency serotonin 5-HT_2A receptor partial agonist, with an affinity (K_i) of 2,502 nM, an EC₅₀Tooltip half-maximal effective concentration of 160 to 3,548 nM (depending on the signaling cascade and study), and an E_maxTooltip maximal efficacy of 66 to 109%.^{[8][9][12][13]} It has also been assessed at several other receptors.^[8][9] In a much earlier study, its affinities (K_i) were 1,020 nM at the serotonin 5-HT₁ receptor and 5,200 nM at the serotonin 5-HT₂ receptor.^[17][18] The drug does not appear to bind to the monoamine transporters, at least at the assessed concentrations (up to 7,000 nM).^[8][9] It was inactive at the human trace amine-associated receptor 1 (TAAR1).^[8][9] 2,5-DMA shows dramatically reduced potency as a serotonin 5-HT_2A receptor agonist compared to the DOx drugs, such as 2,5-dimethoxy-4-methylamphetamine (DOM).^[8][9]

2,5-DMA produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.^[7] However, it produces a very weak head-twitch response compared to other structurally related psychedelics like DOM, DOET, DOPR, and even DOBU.^[7] In addition, it is less potent in comparison.^[7] 2,5-DMA substitutes for DOM in rodent drug discrimination tests, albeit with dramatically lower potency than other DOx drugs.^[19] It also substitutes for 5-MeO-DMT in rodent drug discrimination tests.^[20] These findings suggesting that 2,5-DMA might produce weak hallucinogenic effects at sufficiently high doses.^[7][19][20] 2,5-DMA shows no substitution for dextroamphetamine in drug discrimination tests, suggesting that it lacks psychostimulant- or amphetamine-like effects, at least in rodents.^[19] Unlike other DOx drugs like DOM, DOPR, DOBU, and DOAM, 2,5-DMA does not produce hyperlocomotion in rodents and instead dose-dependently produces only hypolocomotion.^[7] On the other hand, it does similarly produce hypothermia at higher doses.^[7]

Though 2,5-DMA appears to be inactive or of very low potency as a psychedelic in humans, it is a highly potent anti-inflammatory drug similarly to other DOx and 2C drugs.^[13][21] This was in spite of it being of very low potency as a serotonin 5-HT_2A receptor agonist in terms of calcium mobilization in the study (EC₅₀ = 3,548 nM; E_max = 109.0%).^[13] Based on the preceding findings, Charles D. Nichols has said that both fully anti-inflammatory non-psychedelic compounds like 2,5-DMA and fully psychedelic non-anti-inflammatory compounds like DOTFM are known.^[21]

Pharmacokinetics

2,5-DMA crosses the blood–brain barrier in rodents.^[7] It showed the lowest brain/plasma ratio among DOM and its higher homologues.^[7]

Synthesis

The chemical synthesis of 2,5-DMA has been described.^[1][2][22]

Analogues and derivatives

Analogues and derivatives of 2,5-DMA include the DOx series like DOM, DOB, and DOI, FLY compounds like DOB-FLY, Bromo-DragonFLY (DOB-DFLY), DOH-5-hemiFLY, 25-NB compounds like DOM-NBOMe, DOB-NBOMe, and DOI-NBOMe, and other compounds like trimethoxyamphetamines (TMAs) and pentamethoxyamphetamine (PeMA).^[1][2] Methoxamine (β-hydroxy-2,5-DMA) is another derivative of 2,5-DMA.^[2]

Manufacturing

2,5-DMA is used by Polaroid Corporation in the manufacturing of Polaroid film.^[3][25][26]

Legal status