3-Methoxyamphetamine

Stimulant drug of the amphetamine class From Wikipedia, the free encyclopedia

3-Methoxyamphetamine (3-MA), also known as meta-methoxyamphetamine (MMA), is a monoamine releasing agent (MRA) of the amphetamine family.^[2]^[3]^[4] It is a positional isomer of para-methoxyamphetamine (PMA; 4-methoxyamphetamine).^[1]^[5] The drug has been encountered as a novel designer drug.^[6]

Other names3-MA; 3-MeO-A; meta-Methoxyamphetamine; MMA

Routes of
administrationOral^[1]

Drug classSerotonin–norepinephrine–dopamine releasing agent

ATC code

None

Quick facts Clinical data, Other names ...

3-Methoxyamphetamine
Clinical data

Other names	3-MA; 3-MeO-A; meta-Methoxyamphetamine; MMA
Routes of administration	Oral^[1]
Drug class	Serotonin–norepinephrine–dopamine releasing agent
ATC code	None
Identifiers
IUPAC name 1-(3-methoxyphenyl)propan-2-amine
CAS Number	17862-85-0^Y
PubChem CID	152234
ChemSpider	134180^Y
UNII	C2B7C98LY8
ChEMBL	ChEMBL16247^Y
CompTox Dashboard (EPA)	DTXSID00939104
Chemical and physical data
Formula	C₁₀H₁₅NO
Molar mass	165.236 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES NC(C)CC1=CC=CC(OC)=C1
InChI InChI=1S/C10H15NO/c1-8(11)6-9-4-3-5-10(7-9)12-2/h3-5,7-8H,6,11H2,1-2H3^Y Key:VEJWNIYARKAHFI-UHFFFAOYSA-N^Y
^NY (what is this?) (verify)

Use and effects

According to Alexander Shulgin, 3-MA showed no central or psychedelic effects in humans at a total dose of 50 mg (25 mg orally twice separated by 3 hours).^[1]^[5] However, sympathomimetic effects have occurred with the drug at an oral dose of 25 mg in humans.^[1]^[7]

Pharmacology

Pharmacodynamics

3-MA has similar effects in animal drug discrimination tests to para-methoxyamphetamine (PMA; 4-MA).^[2] However, it has a different balance of monoamine release, being a combined serotonin–norepinephrine–dopamine releasing agent (SNDRA) rather than a fairly selective serotonin releasing agent (SSRA) like PMA.^[8]^[3]^[9] 3-MA's EC₅₀Tooltip half-maximal effective concentration values for induction of monoamine release are 58.0 nM for norepinephrine and 103 nM for dopamine in rat brain synaptosomes, whereas the value for serotonin was not reported.^[8]

The drug has shown relatively low affinity for serotonin receptors in the rat stomach fundus strip, intermediate between amphetamine and amphetamine psychedelics like DOM and DOB.^[10]^[11] In another study, its affinities (K_i) for the serotonin 5-HT₁ and 5-HT₂ receptors were 2,660 nM and 7,850 nM, respectively.^[12] 3-MA is also a weak agonist of the human trace amine-associated receptor 1 (TAAR1), with micromolar potency.^[13]

3-MA produced hyperlocomotion, a psychostimulant-like effect, in rodents similarly to amphetamine and PMA.^[14]^[15] It also produced hyperthermia and myoclonus, which are serotonin syndrome-associated effects, in rodents similarly to PMA.^[14]^[15]

3-MA produces gepefrine (3-hydroxyamphetamine), a sympathomimetic agent, as one of its major metabolites.^[16]

Chemistry

Analogues

The 2-aminoindane analogue of 3-MA is 5-methoxy-2-aminoindane (MEAI; 5-MeO-AI).^[17]

History

3-MA has appeared on the illicit market as a designer drug alternative to MDMA similarly PMA in the late 1980s and early 1990s, although far more rarely than PMA.^[6]^[18] Subsequently, it reappeared on the market, specifically via online sellers, in December 2021.^[6]

References

[1]
Shulgin A, Manning T, Daley PF (2011). "#75. 3-MA (3-Methoxyamphetamine)". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. pp. 158–161. ISBN 978-0-9630096-3-0. 3-MA has a transient pressor effect on humans. The minimal effective dose on oral administration was 25 mg. No tachycardia or sustained elevation of blood pressure (Schelling et al., 1974). [...] No psychedelic activity was detected in humans at 50 mg (2 x 25 mg doses, separated by three hours) (Shulgin and Shulgin, 1991).
[2]
Glennon RA, Young R, Hauck AE (May 1985). "Structure-activity studies on methoxy-substituted phenylisopropylamines using drug discrimination methodology". Pharmacology, Biochemistry, and Behavior. 22 (5): 723–729. doi:10.1016/0091-3057(85)90520-9. PMID 3839309. S2CID 22341227.
[3]
Tseng LF, Menon MK, Loh HH (May 1976). "Comparative actions of monomethoxyamphetamines on the release and uptake of biogenic amines in brain tissue". The Journal of Pharmacology and Experimental Therapeutics. 197 (2): 263–271. PMID 1271280.
[4]
GB 1527479, "Acid Addition Salts of D-(+)-1-(3-Hydroxyphenyl)-2-Aminopropane and Their Manufacture and Use"
[5]
Shulgin AT, Shulgin A (1991). PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. ISBN 9780963009609. OCLC 25627628. The two positional analogues of 4-MA are known; vis., 2-MA and 3-MA. [...] The meta-compound, 3-MA, has been metabolically explored in man, but no central effects were noted at a 50 milligram dose (2x25 milligrams, separated by three hours). There appears to be no report of any human trial of 2-MA. The N-methyl homologue of 2-MA is a commercial adrenergic bronchodilator called Methoxyphenamine, or Orthoxine. It has been used in the prevention of acute asthma attacks in doses of up to 200 milligrams, with only slight central stimulation. The N-methyl homologues of 3-MA and 4-MA are known, and the latter compound is the stuff of a separate entry in this book.
[6]
"м-Метоксиамфетамин (3-Methoxyamphetamine)". АИПСИН (in Russian). Retrieved 1 January 2026.
[7]
Schelling, J.L., Dufour, R.J., Jequier, E. (1974) Vasopressor effect of 3-methoxyamphetamine in man. Vortr. Symp. Meeting Date 1970, pp 175-183. "Like other amphetamines, 3-methoxyamphetamine (I) [17862-85-0] had a transient pressor effect on man. The minimal effective dose on oral administration was 25 mg. Differences between that dose and a placebo were significant in young normotensive subjects. The acute response of older patients with chronic hypotension to the same dose was unpredictable. Unlike other amphetamines, this drug did not produce any tachycardia. There was no sustained elevation of blood pressure when the drug was given twice daily for 3 days. The urinary excretion of catechol amines was unchanged."
[8]
Blough B (July 2008). "Dopamine-releasing agents" (PDF). In Trudell ML, Izenwasser S (eds.). Dopamine Transporters: Chemistry, Biology and Pharmacology. Hoboken [NJ]: Wiley. pp. 305–320. ISBN 978-0-470-11790-3. OCLC 181862653. OL 18589888W.
[9]
Menon MK, Tseng LF, Loh HH (May 1976). "Pharmacological evidence for the central serotonergic effects of monomethoxyamphetamines". The Journal of Pharmacology and Experimental Therapeutics. 197 (2): 272–9. PMID 946817.
[10]
Domelsmith LN, Eaton TA, Houk KN, Anderson GM, Glennon RA, Shulgin AT, Castagnoli N, Kollman PA (December 1981). "Photoelectron spectra of psychotropic drugs. 6. Relationships between the physical properties and pharmacological actions of amphetamine analogues". J Med Chem. 24 (12): 1414–1421. doi:10.1021/jm00144a009. PMID 7310818.
[11]
Glennon RA, Liebowitz SM, Anderson GM (March 1980). "Serotonin receptor affinities of psychoactive phenalkylamine analogues". J Med Chem. 23 (3): 294–299. doi:10.1021/jm00177a017. PMID 7365744.
[12]
Glennon RA (January 1987). "Central serotonin receptors as targets for drug research". J Med Chem. 30 (1): 1–12. doi:10.1021/jm00384a001. PMID 3543362. Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites
[13]
Lewin AH, Miller GM, Gilmour B (December 2011). "Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class". Bioorg Med Chem. 19 (23): 7044–7048. doi:10.1016/j.bmc.2011.10.007. PMC 3236098. PMID 22037049.
[14]
Loh HH, Tseng LF (1978). "Role of biogenic amines in the actions of monomethoxyamphetamines". In Stillman R, Willette R (eds.). The Psychopharmacology of Hallucinogens. Pergamon. pp. 13–22. ISBN 978-1-4831-4606-5. Retrieved 16 January 2025. d,l-p-Methoxyamphetamine (I) [23239-32-9] was more effective than d,l-o-methoxyamphetamine [52850-78-9], d,l-m-methoxyamphetamine [17862-91-8], or d-amphetamine [51-64-9] in blocking the uptake or increasing the release of 5-hydroxytryptamine [50-67-9] by brain tissue slices. Amphetamine was more effective than the methoxy analogs in increasing the release or blocking the uptake of dopamine [51-61-6] or norepinephrine [51-41-2]. I was less effective than the m-isomer in affecting the release and uptake of dopamine. The o-isomer was the least effective of all 3 biogenic amines. Amphetamine and the p- and m- (but not the o-) methoxy compds. increased myoclonic twitch activity in rats. In addn., I and m-methoxyamphetamine stimulated locomotor activity, whereas the o-isomer did not. I was 10 times more effective than amphetamine in increasing the release of 5-hydroxytryptamine by the rat brain in vivo. This effect of I did not appear to be due to inhibition of 5-hydroxytryptamine uptake. The neuronal 5-hydroxytryptamine uptake inhibitor chlorimipramine inhibited the effect of I on food-reinforced and locomotor behavior and on myoclonic twitch activity.
[15]
Menon MK, Tseng LF, Loh HH (May 1976). "Pharmacological evidence for the central serotonergic effects of monomethoxyamphetamines". J Pharmacol Exp Ther. 197 (2): 272–279. PMID 946817. The effects of dl-para-methoxyamphetamine-HCl (dl-PMA) [52740-56-4], dl-meta-methoxyamphetamine-HCl (dl-MMA) [54376-87-3] and dl-ortho-methoxyamphetamine (dl-OMA) [52850-78-9], and d-amphetamine sulfate (d-A) [51-63-8] on the myoclonic twitch activity (MTA) of suprahyoideal muscle in rats and locomotor activity in rats and mice were studied. PMA, MMA and d-A increased the MTA but OMA was ineffective. The increased MTA induced by d-A was not influenced by the blockade of 5-hydroxytryptamine (5-HT) [50-67-9] receptor by methysergide or inhibition of 5-HT synthesis by para-chlorophenylalanine (PCPA) but was reduced by haloperidol which blocked the dopamine [51-61-6] receptor. On the other hand, the increased MTA produced by PMA was not influenced by haloperidol but was reduced by methysergide and PCPA. The increased MTA induced by MMA was not effectively blocked by either PCPA or haloperidol but was blocked by the combination of both PCPA and haloperidol. The results indicate that whereas the increased MTA produced by d-A is not dependent on the availability of 5-HT, PMA exerts its effect by a release of 5-HT and that the MMA effect is due to a release of both 5-HT and dopamine. High doses of PMA and MMA increased the locomotor activity and produced hyperthermia but OMA was inactive. The findings are in agreement with previous biochem. findings that PMA releases 5-HT in brain tissue and suggests that PMA exerts it pharmacol. effects by releasing 5-HT.
[16]
Midha KK, Cooper JK, Bailey K, Hubbard JW (February 1981). "The metabolism of 3-methoxyamphetamine in dog, monkey and man". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 11 (2): 137–146. doi:10.3109/00498258109045284. PMID 6894510.
[17]
Nichols DE, Marona-Lewicka D, Huang X, Johnson MP (1993). "Novel serotonergic agents". Drug des Discov. 9 (3–4): 299–312. PMID 8400010.
[18]
Dal Cason TA (June 2001). "A re-examination of the mono-methoxy positional ring isomers of amphetamine, methamphetamine and phenyl-2-propanone". Forensic Science International. 119 (2): 168–194. doi:10.1016/S0379-0738(00)00425-4. PMID 11376983.