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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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| Formula | C10H15NO |
| Molar mass | 165.236 g·mol−1 |
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3-Methoxyamphetamine (3-MA), also known asmeta-methoxyamphetamine (MMA), is amonoamine releasing agent (MRA) of theamphetamine family.[2][3][4] It is apositional isomer ofpara-methoxyamphetamine (PMA; 4-methoxyamphetamine).[1][5] The drug has been encountered as a noveldesigner drug.[6]
According toAlexander Shulgin, 3-MA showed nocentral orpsychedelic effects in humans at a total dose of 50 mg (25 mgorally 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]
3-MA has similar effects in animaldrug discrimination tests topara-methoxyamphetamine (PMA; 4-MA).[2] However, it has a different balance ofmonoamine release, being a combinedserotonin–norepinephrine–dopamine releasing agent (SNDRA) rather than a fairlyselectiveserotonin releasing agent (SSRA) like PMA.[8][3][9] 3-MA'sEC50Tooltip half-maximal effective concentration values for induction of monoamine release are 58.0 nM fornorepinephrine and 103 nM fordopamine in rat brainsynaptosomes, whereas the value forserotonin was not reported.[8]
The drug has shown relatively lowaffinity forserotonin receptors in the rat stomach fundus strip, intermediate betweenamphetamine and amphetaminepsychedelics likeDOM andDOB.[10][11] In another study, its affinities (Ki) for the serotonin5-HT1 and5-HT2 receptors were 2,660 nM and 7,850 nM, respectively.[12] 3-MA is also a weakagonist of the humantrace amine-associated receptor 1 (TAAR1), withmicromolarpotency.[13]
3-MA producedhyperlocomotion, apsychostimulant-like effect, in rodents similarly toamphetamine and PMA.[14][15] It also producedhyperthermia andmyoclonus, which areserotonin syndrome-associated effects, in rodents similarly to PMA.[14][15]
3-MA producesgepefrine (3-hydroxyamphetamine), asympathomimetic agent, as one of its majormetabolites.[16]
The2-aminoindaneanalogue of 3-MA is5-methoxy-2-aminoindane (MEAI; 5-MeO-AI).[17]
3-MA has appeared on the illicit market as adesigner drug alternative toMDMA 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]
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.
