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Other names | 3-MA; 3-MeO-A; meta-Methoxyamphetamine; MMA |
Routes of administration | Oral [1] |
Drug class | Serotonin–norepinephrine–dopamine releasing agent |
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Chemical and physical data | |
Formula | C10H15NO |
Molar mass | 165.236 g·mol−1 |
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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]
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] [6]
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. [7] [3] [8] 3-MA's EC50 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. [7]
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. [9] [10] In another study, its affinities (Ki) for the serotonin 5-HT1 and 5-HT2 receptors were 2,660 nM and 7,850 nM, respectively. [11] 3-MA is also a weak agonist of the human trace amine-associated receptor 1 (TAAR1), with micromolar potency. [12]
3-MA produced hyperlocomotion, a psychostimulant-like effect, in rodents similarly to amphetamine and PMA. [13] [14] It also produced hyperthermia and myoclonus, serotonin-associated effects, in rodents similarly to PMA. [13] [14]
3-MA produces gepefrine (3-hydroxyamphetamine), a sympathomimetic agent, as one of its major metabolites. [15]
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. [16]
The 2-aminoindane analogue of 3-MA is 5-methoxy-2-aminoindane (MEAI; 5-MeO-AI). [17]
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).
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.
Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites
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.
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.