3-Methoxyamphetamine

Last updated
3-Methoxyamphetamine
3-Methoxyamphetamine.png
Clinical data
Other names3-MA; 3-MeO-A; meta-Methoxyamphetamine; MMA
Routes of
administration 		Oral [1]
Drug class Serotonin–norepinephrine–dopamine releasing agent
ATC code
  • None
Identifiers
  • 1-(3-methoxyphenyl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C10H15NO
Molar mass 165.236 g·mol−1
3D model (JSmol)
  • NC(C)CC1=CC=CC(OC)=C1
  • InChI=1S/C10H15NO/c1-8(11)6-9-4-3-5-10(7-9)12-2/h3-5,7-8H,6,11H2,1-2H3 Yes check.svgY
  • Key:VEJWNIYARKAHFI-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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]

3-MA has similar effects in animal drug discrimination tests to PMA. [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. [6] [3] [7] 3-MA's EC50 Tooltip 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. [6] 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. [8] [9] 3-MA is also a weak agonist of the human trace amine-associated receptor 1 (TAAR1), with micromolar potency. [10]

3-MA produced hyperlocomotion, a psychostimulant-like effect, in rodents similarly to amphetamine and PMA. [11] [12] It also produced hyperthermia and myoclonus, serotonin-associated effects, in rodents similarly to PMA. [11] [12] 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] [13] It produces gepefrine (3-hydroxyamphetamine), a sympathomimetic agent, as one of its major metabolites. [14]

3-MA has appeared on the illicit market as a designer drug alternative to MDMA similarly PMA, although far more rarely than its infamous positional isomer. [15]

The 2-aminoindane analogue of 3-MA is 5-methoxy-2-aminoindane (MEAI; 5-MeO-AI). [16]

See also

Related Research Articles

α-Methyltryptamine Chemical compound

α-Methyltryptamine is a psychedelic, stimulant, and entactogen drug of the tryptamine family. It was originally developed as an antidepressant at Upjohn in the 1960s, and was used briefly as an antidepressant in the Soviet Union under the brand name Indopan or Indopane before being discontinued.

<i>para</i>-Methoxyamphetamine Chemical compound

para-Methoxyamphetamine (PMA), also known as 4-methoxyamphetamine (4-MA), is a designer drug of the amphetamine class with serotonergic effects. Unlike other similar drugs of this family, PMA does not produce stimulant, euphoriant, or entactogen effects, and behaves more like an antidepressant in comparison, though it does have some psychedelic properties.

<span class="mw-page-title-main">Phenmetrazine</span> Chemical compound

Phenmetrazine, sold under the brand name Preludin among others, is a stimulant drug first synthesized in 1952 and originally used as an appetite suppressant, but withdrawn from the market in the 1980s due to widespread misuse. It was initially replaced by its analogue phendimetrazine which functions as a prodrug to phenmetrazine, but now it is rarely prescribed, due to concerns of misuse and addiction. Chemically, phenmetrazine is a substituted amphetamine containing a morpholine ring or a substituted phenylmorpholine.

<span class="mw-page-title-main">4-Methylaminorex</span> Group of stereoisomers

4-Methylaminorex is a stimulant drug of the 2-amino-5-aryloxazoline group that was first synthesized in 1960 by McNeil Laboratories. It is also known by its street name "U4Euh" ("Euphoria"). It is banned in many countries as a stimulant. 4-Methylaminorex has effects comparable to methamphetamine but with a longer duration.

<span class="mw-page-title-main">4-Methylthioamphetamine</span> Chemical compound

4-Methylthioamphetamine (4-MTA) is a designer drug of the substituted amphetamine class developed in the 1990s by a team led by David E. Nichols, an American pharmacologist and medical chemist, at Purdue University. It acts as a non-neurotoxic highly selective serotonin releasing agent (SSRA) in animals. 4-MTA is the methylthio derivative of amphetamine.

<span class="mw-page-title-main">Chlorphentermine</span> Weight loss medication

Chlorphentermine, sold under the brand names Apsedon, Desopimon, and Lucofen, is a serotonergic appetite suppressant of the amphetamine family. Developed in 1962, it is the para-chloro derivative of the better-known appetite suppressant phentermine, which is still in current use.

<i>para</i>-Methoxy-<i>N</i>-methylamphetamine Stimulant and psychedelic designer drug

para-Methoxy-N-methylamphetamine, chemically known as methyl-MA, 4-methoxy-N-methylamphetamine, and 4-MMA is a stimulant and psychedelic drug closely related to the amphetamine-class serotonergic drug para-methoxyamphetamine (PMA). PMMA is the 4-methoxy analog of methamphetamine. Little is known about the pharmacological properties, metabolism, and toxicity of PMMA; because of its structural similarity to PMA, which has known toxicity in humans, it is thought to have considerable potential to cause harmful side effects or death in overdose. In the early 2010s, a number of deaths in users of the drug MDMA were linked to misrepresented tablets and capsules of PMMA.

<span class="mw-page-title-main">Naphthylaminopropane</span> Chemical compound

Naphthylaminopropane, also known as naphthylisopropylamine (NIPA), is an experimental drug that was under investigation for the treatment of alcohol and stimulant addiction.

<span class="mw-page-title-main">MMDA-2</span> Psychedelic drug

MMDA-2 (2-methoxy-4,5-methylenedioxyamphetamine) is a psychedelic drug of the amphetamine class. It is closely related to MMDA and MDA.

<span class="mw-page-title-main">Norfenfluramine</span> Never-marketed drug of the amphetamine family

Norfenfluramine, or 3-trifluoromethylamphetamine, is a never-marketed drug of the amphetamine family and a major active metabolite of the appetite suppressants fenfluramine and benfluorex. The compound is a racemic mixture of two enantiomers with differing activities, dexnorfenfluramine and levonorfenfluramine.

<i>para</i>-Chloroamphetamine Chemical compound

para-Chloroamphetamine (PCA), also known as 4-chloroamphetamine (4-CA), is a serotonin–norepinephrine–dopamine releasing agent (SNDRA) and serotonergic neurotoxin of the amphetamine family. It is used in scientific research in the study of the serotonin system, as a serotonin releasing agent (SRA) at lower doses to produce serotonergic effects, and as a serotonergic neurotoxin at higher doses to produce long-lasting depletions of serotonin.

<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitters and hence enhanced signaling by those neurotransmitters. The monoamine neurotransmitters include serotonin, norepinephrine, and dopamine; MRAs can induce the release of one or more of these neurotransmitters.

<span class="mw-page-title-main">3-Methoxy-4-methylamphetamine</span> Entactogen and psychedelic drug of the phenethylamine and amphetamine classes

3-Methoxy-4-methylamphetamine (MMA) is an entactogen and psychedelic drug of the phenethylamine and amphetamine classes. It was first synthesized in 1970 and was encountered as a street drug in Italy in the same decade. MMA was largely forgotten until being reassayed by David E. Nichols as a non-neurotoxic MDMA analogue in 1991, and has subsequently been sold as a designer drug on the internet since the late 2000s.

<span class="mw-page-title-main">MMAI</span> Chemical compound

5-Methoxy-6-methyl-2-aminoindane (MMAI) is a drug of the 2-aminoindane group developed in the 1990s by a team led by David E. Nichols at Purdue University. It acts as a less neurotoxic and highly selective serotonin releasing agent (SSRA) and produces entactogenic effects in humans. It has been sold as a designer drug and research chemical online since 2010.

<span class="mw-page-title-main">Serotonin releasing agent</span> Class of compounds

A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons, including dopamine and norepinephrine neurons.

<span class="mw-page-title-main">4-Methylamphetamine</span> Stimulant and anorectic drug of the amphetamine class

4-Methylamphetamine (4-MA), also known by the former proposed brand name Aptrol, is a stimulant and anorectic drug of the amphetamine family. It is structurally related to mephedrone (4-methylmethcathinone).

<span class="mw-page-title-main">4-Methylmethamphetamine</span> Stimulant and entactogen drug of the amphetamine class

4-Methylmethamphetamine (4-MMA), also known as mephedrine, is a putative stimulant and entactogen drug of the amphetamine family. It acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA). The drug is the β-deketo analogue of mephedrone and the N-methyl analogue of 4-methylamphetamine (4-MA).

<span class="mw-page-title-main">2-Methoxyamphetamine</span> Chemical compound

2-Methoxyamphetamine (2-MA), also known as ortho-methoxyamphetamine (OMA), is a drug of the amphetamine class. It is substantially weaker in inhibiting the reuptake of and inducing the release of the monoamine neurotransmitters compared to related agents such as amphetamine, MMA, and PMA, and may instead act as a β-adrenergic receptor agonist similarly to its N-methylated analogue methoxyphenamine.

<i>para</i>-Bromomethamphetamine Pharmaceutical compound

para-Bromomethamphetamine, also known as 4-bromomethamphetamine (4-BMA), is a monoaminergic drug of the amphetamine family related to para-chloroamphetamine. It was studied by József Knoll and colleagues in the 1970s and 1980s.

<span class="mw-page-title-main">4-Methylthiomethamphetamine</span> Pharmaceutical compound

4-Methylthiomethamphetamine, also known as N-methyl-4-methylthioamphetamine (NMMTA), is a monoamine releasing agent (MRA) of the amphetamine family related to 4-methylthioamphetamine (4-MTA) and N,N-dimethyl-4-methylthioamphetamine. Much less is known about 4-MTMA compared to 4-MTA.

References

  1. 1 2 3 4 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. 1 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. 1 2 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. 1 2 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. 1 2 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. 1 2 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.
  12. 1 2 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.
  13. ↑ 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."
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ Nichols DE, Marona-Lewicka D, Huang X, Johnson MP (1993). "Novel serotonergic agents". Drug des Discov. 9 (3–4): 299–312. PMID   8400010.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.