Editing Α-Methyltryptamine (section)

==Pharmacology==
===Pharmacodynamics===
αMT acts as a relatively balanced [[reuptake inhibitor]] and [[releasing agent]] of the main three [[monoamines]]; [[serotonin]], [[norepinephrine]], and [[dopamine]],<ref name="pmid17223101">{{cite journal | vauthors = Nagai F, Nonaka R, Satoh Hisashi Kamimura K | title = The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain | journal = European Journal of Pharmacology | volume = 559 | issue = 2–3 | pages = 132–137 | date = March 2007 | pmid = 17223101 | doi = 10.1016/j.ejphar.2006.11.075 }}</ref> and as a non-[[binding selectivity|selective]] [[serotonin receptor]] [[agonist]].<ref name="pmid18057721">{{cite journal | vauthors = Nonaka R, Nagai F, Ogata A, Satoh K | title = In vitro screening of psychoactive drugs by [(35)S]GTPgammaS binding in rat brain membranes | journal = Biological & Pharmaceutical Bulletin | volume = 30 | issue = 12 | pages = 2328–2333 | date = December 2007 | pmid = 18057721 | doi = 10.1248/bpb.30.2328 | doi-access = free }}</ref>

{| class="wikitable floatright" style="font-size:small;"
|+ Activities of αMT and related compounds
|-
! rowspan="2" | Compound !! colspan="3" | [[Monoamine releasing agent|Monoamine release]] ({{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}}, nM) !! colspan="2" | [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] [[agonist|agonism]]
|-
! [[Serotonin releasing agent|Serotonin]] !! [[Dopamine releasing agent|Dopamine]] !! [[Norepinephrine releasing agent|Norepinephrine]] !! {{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}} (nM) !! [[Intrinsic activity|E<sub>max</sub>]] (%)
|-
| [[Tryptamine]]<!-- T; PAL-235 --> || 33 || 164 || 716 || 7.4 || 104
|-
| [[5-Hydroxytryptamine|Serotonin]]<!-- 5-HT --> || 44 || >10,000 || >10,000 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}}
|-
| [[N,N-Dimethyltryptamine|''N'',''N''-DMT]] || 114 || >10,000 || 4,166 || 38 || 83
|-
| αMT<!-- PAL-17 --> || 22–68 || 79–112 || 79–180 || 23 || 103
|-
| [[α-Ethyltryptamine|αET]]<!-- (±)-αET; (RS)-αET; PAL-125 --> || 23 || 232 || 640 ({{Abbrlink|E<sub>max</sub>|maximal efficacy}} = 78%) || >10,000 || 21
|-
| [[5-MeO-αMT]] || 460 || 8,900 || 1,500 || 2.0–8.4<!-- See 5-MeO-AMT page for sources --> || {{Abbr|ND|No data}}
|-
| [[3,4-Methylenedioxy-N-methylamphetamine|MDMA]] || 57 || 376 || 77 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}}
|- class="sortbottom"
| colspan="6" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' The smaller the value, the more strongly the compound produces the effect. '''Refs:''' <ref name="GlennonDukat2023" /><ref name="BloughLandavazo2014" /><ref name="BloughLandavazoDecker2014">{{cite journal | vauthors = Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB | title = Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes | journal = Psychopharmacology (Berl) | volume = 231 | issue = 21 | pages = 4135–4144 | date = October 2014 | pmid = 24800892 | pmc = 4194234 | doi = 10.1007/s00213-014-3557-7 | url = }}</ref><ref name="RothmanBaumann2003">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur J Pharmacol | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 | url = }}</ref><ref name="NagaiNonakaSatohHisashiKamimura2007">{{cite journal | vauthors = Nagai F, Nonaka R, Satoh Hisashi Kamimura K | title = The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain | journal = Eur J Pharmacol | volume = 559 | issue = 2–3 | pages = 132–137 | date = March 2007 | pmid = 17223101 | doi = 10.1016/j.ejphar.2006.11.075 | url = }}</ref>
|}

====Monoamine oxidase inhibition====
αMT has been shown as a [[reversible reaction|reversible]] [[enzyme inhibitor|inhibitor]] of the [[enzyme]] [[monoamine oxidase]] (MAO) ''[[in vitro]]''<ref>{{cite journal | vauthors = Arai Y, Toyoshima Y, Kinemuchi H | title = Studies of monoamine oxidase and semicarbazide-sensitive amine oxidase. II. Inhibition by alpha-methylated substrate-analogue monoamines, alpha-methyltryptamine, alpha-methylbenzylamine and two enantiomers of alpha-methylbenzylamine | journal = Japanese Journal of Pharmacology | volume = 41 | issue = 2 | pages = 191–197 | date = June 1986 | pmid = 3747266 | doi = 10.1254/jjp.41.191 | doi-access = free }}</ref> and ''[[in vivo]]''.<ref>{{cite journal | vauthors = Greig ME, Walk RA, Gibbons AJ | title = The effect of three tryptamine derivatives on serotonin metabolism in vitro and in vivo | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 127 | pages = 110–115 | date = October 1959 | pmid = 13851725 | url = http://jpet.aspetjournals.org/content/127/2/110.short }}</ref> In rats, the potency of αMT as an MAO-A inhibitor in the brain was approximately equal to that of [[harmaline]] at equimolar doses.{{refn|group=note|MAOI potency was comparable at 7{{nbsp}}μM/kg, equivalent to 1.5{{nbsp}}mg/kg of Harmaline and 1.2{{nbsp}}mg/kg of αMT. At 70{{nbsp}}μM/kg αMT was a much less effective MAOI than harmaline.<ref name="GeyPletscher1961">{{cite journal | vauthors = Gey KF, Pletscher A | title = Effect of alpha-alkylated tryptamine derivatives on 5-hydroxytryptamine metabolism in vivo | journal = British Journal of Pharmacology and Chemotherapy | volume = 19 | issue = 1 | pages = 161–167 | date = August 1962 | pmid = 13898151 | pmc = 1482243 | doi = 10.1111/j.1476-5381.1962.tb01437.x }}</ref>}} Dextroamphetamine did not enhance the [[5-hydroxytryptophan]]-induced rise of serotonin at any level.<ref name="GeyPletscher1961"/> The {{Abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}} of αMT for inhibition of MAO-A has been found to be 380{{nbsp}}nM.<ref name="WagmannBrandtKavanagh2017">{{cite journal | vauthors = Wagmann L, Brandt SD, Kavanagh PV, Maurer HH, Meyer MR | title = In vitro monoamine oxidase inhibition potential of alpha-methyltryptamine analog new psychoactive substances for assessing possible toxic risks | journal = Toxicol Lett | volume = 272 | issue = | pages = 84–93 | date = April 2017 | pmid = 28302559 | doi = 10.1016/j.toxlet.2017.03.007 | url = https://researchonline.ljmu.ac.uk/id/eprint/5909/1/TOXLET-D-17-00086R1_accepted_uncorected.pdf}}</ref> This is similar to that of agents like [[para-methoxyamphetamine|''para''-methoxyamphetamine]] (PMA) and [[4-methylthioamphetamine]] (4-MTA).<ref name="Reyes-ParadaIturriaga-VasquezCassels2019">{{cite journal | vauthors = Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK | title = Amphetamine Derivatives as Monoamine Oxidase Inhibitors | journal = Front Pharmacol | volume = 10 | issue = | pages = 1590 | date = 2019 | pmid = 32038257 | pmc = 6989591 | doi = 10.3389/fphar.2019.01590 | doi-access = free | url = }}</ref>

====Serotonergic neurotoxicity====
A close [[structural analog|analogue]] of αMT, [[Alpha-Ethyltryptamine|α-ethyltryptamine]] (αET), is known to be a [[monoamine neurotoxin|serotonergic neurotoxin]] similarly to [[MDMA]] and [[para-chloroamphetamine|''para''-chloroamphetamine]] (PCA).<ref name="Oeri2021">{{cite journal | vauthors = Oeri HE | title = Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy | journal = Journal of Psychopharmacology | volume = 35 | issue = 5 | pages = 512–536 | date = May 2021 | pmid = 32909493 | pmc = 8155739 | doi = 10.1177/0269881120920420 }}</ref><ref name="GlennonDukat2023">{{cite journal | vauthors = Glennon RA, Dukat MG | title = α-Ethyltryptamine: A Ratiocinatory Review of a Forgotten Antidepressant | journal = ACS Pharmacology & Translational Science | volume = 6 | issue = 12 | pages = 1780–1789 | date = December 2023 | pmid = 38093842 | doi = 10.1021/acsptsci.3c00139 | pmc = 10714429 }}</ref><ref name="HuangJohnsonNichols1991">{{cite journal | vauthors = Huang XM, Johnson MP, Nichols DE | title = Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase) | journal = European Journal of Pharmacology | volume = 200 | issue = 1 | pages = 187–190 | date = July 1991 | pmid = 1722753 | doi = 10.1016/0014-2999(91)90686-k }}</ref>

===Pharmacokinetics===
2-Oxo-αMT, 6-hydroxy-αMT, 7-hydroxy-αMT, and 1′-hydroxy-αMT were detected as [[metabolite]]s of αMT in male [[Laboratory rat|Wistar rats]].<ref name="Barceloux2012" /><ref name="Szara1961">{{cite journal | vauthors = Szara S | title = 6-Hydroxylation: an important metabolic route for alpha-methyltryptamine | journal = Experientia | volume = 17 | issue = 2 | pages = 76–77 | date = February 1961 | pmid = 13774483 | doi = 10.1007/BF02171429 | s2cid = 27030395 | doi-access = free }}</ref><ref name="KanamoriKuwayamaTsujikawa2008">{{cite journal | vauthors = Kanamori T, Kuwayama K, Tsujikawa K, Miyaguchi H, Iwata YT, Inoue H | title = In vivo metabolism of alpha-methyltryptamine in rats: identification of urinary metabolites | journal = Xenobiotica; the Fate of Foreign Compounds in Biological Systems | volume = 38 | issue = 12 | pages = 1476–1486 | date = December 2008 | pmid = 18982537 | doi = 10.1080/00498250802491654 | s2cid = 20637936 }}</ref>