Editing 5-MeO-AMT (section)

==Pharmacology==
===Pharmacodynamics===
{| class="wikitable floatright" style="font-size:small;"
|+ 5-MeO-AMT activities
|-
! [[Biological target|Target]]
! [[Affinity (pharmacology)|Affinity]] (K<sub>i</sub>, nM)
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]]
| 46–194 (K<sub>i</sub>)<br />680 ({{Abbrlink|EC<sub>50</sub>|Half-maximal effective concentration}})<br />101% ({{Abbrlink|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT1B receptor|5-HT<sub>1B</sub>]]
| 417 (rat)
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]]
| 3.1–34 (K<sub>i</sub>)<br />2–8.4 ({{Abbr|EC<sub>50</sub>|Half-maximal effective concentration}})<br />84% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]]
| 4 ({{Abbr|EC<sub>50</sub>|Half-maximal effective concentration}})
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]]
| 90
|-
| [[Alpha-1A adrenergic receptor|α<sub>1A</sub>]]
| >12,000
|-
| [[Alpha-2A adrenergic receptor|α<sub>2A</sub>]]
| 11,000
|-
| [[D1 receptor|D<sub>1</sub>]]
| >25,000
|-
| [[D2 receptor|D<sub>2</sub>]]
| >25,000
|-
| [[D3 receptor|D<sub>3</sub>]]
| >25,000
|-
| [[H1 receptor|H<sub>1</sub>]]
| >25,000
|-
| [[TAAR1|TAAR<sub>1</sub>]]
| 1,100 (K<sub>i</sub>) (rat)<br />4,800 (K<sub>i</sub>) (mouse)<br />>10,000 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) (human)
|-
| {{Abbrlink|SERT|Serotonin transporter}}
| 8,270–12,000 (K<sub>i</sub>)<br />1,980–17,000 ({{Abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />460 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})
|-
| {{Abbrlink|NET|Norepinephrine transporter}}
| >22,000 (K<sub>i</sub>)<br />37,000–78,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />8,900 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})
|-
| {{Abbrlink|DAT|Dopamine transporter}}
| >26,000 (K<sub>i</sub>)<br />2,690–43,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />1,500 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})
|-
| {{Abbrlink|MAO-A|Monoamine oxidase A}}
| 31,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})
|- class="sortbottom"
| colspan="2" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. '''Refs:''' <ref name="BindingDB">{{cite journal | vauthors = Liu T | title=BindingDB BDBM50227458 CHEMBL2093088 | journal=Journal of Medicinal Chemistry | date=1988 | volume=31 | issue=7 | pages=1406–1412 | doi=10.1021/jm00402a026 | pmid=3385733 | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50227458 | access-date=29 November 2024| url-access=subscription }}</ref><ref name="RickliMoningHoener2016">{{cite journal | vauthors = Rickli A, Moning OD, Hoener MC, Liechti ME | title = Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens | journal = European Neuropsychopharmacology | volume = 26 | issue = 8 | pages = 1327–1337 | date = August 2016 | pmid = 27216487 | doi = 10.1016/j.euroneuro.2016.05.001 | s2cid = 6685927 | url = http://edoc.unibas.ch/53326/1/20170117174852_587e4af45b658.pdf }}</ref><ref name="GatchForsterJanowsky2011" /><ref name="NagaiNonakaKamimura2007" /><ref name="WangZhuPaudel2023">{{cite journal | vauthors = Wang S, Zhu A, Paudel S, Jang CG, Lee YS, Kim KM | title = Structure-Activity Relationship and Evaluation of Phenethylamine and Tryptamine Derivatives for Affinity towards 5-Hydroxytryptamine Type 2A Receptor | journal = Biomol Ther (Seoul) | volume = 31 | issue = 2 | pages = 176–182 | date = March 2023 | pmid = 36224112 | pmc = 9970836 | doi = 10.4062/biomolther.2022.096 | url = }}</ref><ref name="WagmannBrandtKavanagh2017" /><ref name="SimmlerBuchyChaboz2016">{{cite journal | vauthors = Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME | title = In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1 | journal = J Pharmacol Exp Ther | volume = 357 | issue = 1 | pages = 134–144 | date = April 2016 | pmid = 26791601 | doi = 10.1124/jpet.115.229765 | url = https://web.archive.org/web/20250509235235/https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA}}</ref>
|}

5-MeO-AMT acts as a [[binding selectivity|non-selective]] [[serotonin receptor agonist]], including of the [[serotonin]] [[5-HT1A receptor|5-HT<sub>1A</sub>]], [[5-HT2A receptor|5-HT<sub>2A</sub>]], and [[5-HT2B receptor|5-HT<sub>2B</sub> receptor]]s, among others.<ref name="GatchForsterJanowsky2011">{{cite journal | vauthors = Gatch MB, Forster MJ, Janowsky A, Eshleman AJ | title = Abuse liability profile of three substituted tryptamines | journal = J Pharmacol Exp Ther | volume = 338 | issue = 1 | pages = 280–289 | date = July 2011 | pmid = 21474568 | pmc = 3126641 | doi = 10.1124/jpet.111.179705 | url = }}</ref><ref name="RickliMoningHoener2016" /> Its {{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}} at the serotonin 5-HT<sub>2A</sub> receptor has been found to be 2 to 8.4{{nbsp}}nM.<ref name="GatchForsterJanowsky2011" /><ref name="RickliMoningHoener2016" /> In relation to this, it is an extremely [[potency (pharmacology)|potent]] agonist of the serotonin 5-HT<sub>2A</sub> receptor ''[[in vitro]]'', showing the highest potency of any other tryptamine assessed in one study.<ref name="RickliMoningHoener2016" /> Its potency in activating the serotonin 5-HT<sub>2A</sub> receptor was 38-fold higher than that of [[dimethyltryptamine]] (DMT) and 361-fold higher than that of [[psilocin]] in the same study.<ref name="RickliMoningHoener2016" /> It is also a highly potent agonist of the serotonin 5-HT<sub>2B</sub> receptor, with an {{Abbr|EC<sub>50</sub>|half-maximal effective concentration}} of 4{{nbsp}}nM.<ref name="RickliMoningHoener2016" />

Whereas [[tryptamine]], [[serotonin]] (5-hydroxytryptamine), and αMT show potent activity as [[monoamine releasing agent]]s, including of [[serotonin]], [[norepinephrine]], and/or [[dopamine]], the monoamine-releasing activity of 5-methoxylated tryptamine derivatives, like [[5-methoxytryptamine]], [[5-MeO-NMT]], and [[5-MeO-DMT]] among others, is dramatically reduced or abolished.<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="BloughLandavazoPartilla2014">{{cite journal | vauthors = Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, Rothman RB | title = Alpha-ethyltryptamines as dual dopamine-serotonin releasers | journal = Bioorg Med Chem Lett | volume = 24 | issue = 19 | pages = 4754–4758 | date = October 2014 | pmid = 25193229 | pmc = 4211607 | doi = 10.1016/j.bmcl.2014.07.062 | url = }}</ref><ref name="RothmanBaumann2006">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Curr Top Med Chem | volume = 6 | issue = 17 | pages = 1845–1859 | date = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = }}</ref><ref name="NagaiNonakaKamimura2007">{{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><ref name="GatchForsterJanowsky2011" /> Accordingly, whereas the {{Abbr|EC<sub>50</sub>|half-maximal effective concentration}} values of αMT for induction of monoamine release are 22 to 68{{nbsp}}nM for serotonin, 79 to 112{{nbsp}}nM for norepinephrine, and 79 to 180{{nbsp}}nM for dopamine, the {{Abbr|EC<sub>50</sub>|half-maximal effective concentration}} values in the case of 5-MeO-AMT are 460{{nbsp}}nM for serotonin, 8,900{{nbsp}}nM for norepinephrine, and 1,500{{nbsp}}nM for dopamine.<ref name="NagaiNonakaKamimura2007" /><ref name="BloughLandavazoPartilla2014" /><ref name="RickliMoningHoener2016" /> Similarly, it is of very low potency as a [[monoamine reuptake inhibitor]] ({{Abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}} values >1,000{{nbsp}}nM).<ref name="NagaiNonakaKamimura2007" /><ref name="RickliMoningHoener2016" /> Considering the very high potency of 5-MeO-AMT in activating the serotonin 5-HT<sub>2A</sub> receptor, its weak activities as a monoamine releasing agent and reuptake inhibitor are of questionable significance.<ref name="NagaiNonakaKamimura2007" /><ref name="BloughLandavazoPartilla2014" /><ref name="RickliMoningHoener2016" /><ref name="GatchForsterJanowsky2011" />

5-MeO-AMT is a weak [[monoamine oxidase A]] (MAO-A) [[monoamine oxidase inhibitor|inhibitor]], with an {{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}} of 31,000{{nbsp}}nM.<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><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> For comparison, the {{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}} of AMT for MAO-A inhibition was 380{{nbsp}}nM (~82-fold more potent than 5-MeO-AMT)<ref name="Reyes-ParadaIturriaga-VasquezCassels2019" /><ref name="WagmannBrandtKavanagh2017" /> and the {{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}} values of [[amphetamine]] (and its [[enantiomer]]s) for MAO-A inhibition have been reported to be 11,000 to 70,000{{nbsp}}nM.<ref name="Reyes-ParadaIturriaga-VasquezCassels2019" />

5-MeO-AMT produces the [[head-twitch response]], a behavioral proxy of [[psychedelic drug|psychedelic]] effects, in rodents, and this is reversed by the serotonin 5-HT<sub>2A</sub> receptor [[receptor antagonist|antagonist]] [[ketanserin]].<ref name="AbieroBotanasSayson2019">{{cite journal | vauthors = Abiero A, Botanas CJ, Sayson LV, Custodio RJ, de la Peña JB, Kim M, Lee HJ, Seo JW, Ryu IS, Chang CM, Yang JS, Lee YS, Jang CG, Kim HJ, Cheong JH | title = 5-Methoxy-α-methyltryptamine (5-MeO-AMT), a tryptamine derivative, induces head-twitch responses in mice through the activation of serotonin receptor 2a in the prefrontal cortex | journal = Behav Brain Res | volume = 359 | issue = | pages = 828–835 | date = February 2019 | pmid = 30053461 | doi = 10.1016/j.bbr.2018.07.020 | url = }}</ref><ref name="HalberstadtChathaKlein2020" /><ref name="MayDantanarayanaZinke2006">{{cite journal | vauthors = May JA, Dantanarayana AP, Zinke PW, McLaughlin MA, Sharif NA | title = 1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity | journal = J Med Chem | volume = 49 | issue = 1 | pages = 318–328 | date = January 2006 | pmid = 16392816 | doi = 10.1021/jm050663x | url = }}</ref> It substitutes for other psychedelics such as [[DOM (drug)|DOM]] and [[LSD]] in animal [[drug discrimination]] tests, but does not substitute for [[entactogen]]s like [[MDMA]] or [[psychostimulant]]s like [[dextromethamphetamine]] or [[cocaine]].<ref name="GlennonJacynoYoung1983">{{cite journal | vauthors = Glennon RA, Jacyno JM, Young R | title = A comparison of the behavioral properties of (+/-)-, (-)-, and (+)-5-methoxy-alpha-methyltryptamine | journal = Biol Psychiatry | volume = 18 | issue = 4 | pages = 493–498 | date = April 1983 | pmid = 6860723 | doi = | url = }}</ref><ref name="GatchForsterJanowsky2011" /> In contrast to other psychedelics, 5-MeO-AMT has been found to not fully substitute for other psychedelics including DOM, LSD, and [[dimethyltryptamine]] (DMT), but did partially generalize to LSD (67% responding).<ref name="GatchForsterJanowsky2011" /> This is analogous to findings with [[5-MeO-DMT]], which has a major serotonin 5-HT<sub>2A</sub> receptor-mediated component to its discriminative stimulus properties.<ref name="ErmakovaDunbarRucker2022">{{cite journal | vauthors = Ermakova AO, Dunbar F, Rucker J, Johnson MW | title = A narrative synthesis of research with 5-MeO-DMT | journal = J Psychopharmacol | volume = 36 | issue = 3 | pages = 273–294 | date = March 2022 | pmid = 34666554 | pmc = 8902691 | doi = 10.1177/02698811211050543 | url = }}</ref><ref name="ShenJiangWinter2010">{{cite journal | vauthors = Shen HW, Jiang XL, Winter JC, Yu AM | title = Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions | journal = Curr Drug Metab | volume = 11 | issue = 8 | pages = 659–666 | date = October 2010 | pmid = 20942780 | pmc = 3028383 | doi = 10.2174/138920010794233495 | url = }}</ref><ref name="WinterFilipinkTimineri2000">{{cite journal | vauthors = Winter JC, Filipink RA, Timineri D, Helsley SE, Rabin RA | title = The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors | journal = Pharmacol Biochem Behav | volume = 65 | issue = 1 | pages = 75–82 | date = January 2000 | pmid = 10638639 | doi = 10.1016/s0091-3057(99)00178-1 | url = }}</ref> 5-MeO-AMT does not produce [[locomotor hyperactivity]], [[behavioral sensitization]], [[conditioned place preference]], or [[self-administration]], further indicating a lack of psychostimulant-like effects as well as [[misuse potential]].<ref name="GatchForsterJanowsky2011" /><ref name="AbieroBotanasSayson2019" /> Instead, 5-MeO-AMT produces [[hypolocomotion]].<ref name="GatchForsterJanowsky2011" /> 5-MeO-AMT is known to produce [[sympathomimetic]] effects, but these effects likely depend on serotonin 5-HT<sub>2A</sub> receptor activation rather than on monoamine release or reuptake inhibition.<ref name="RickliMoningHoener2016" /> Other serotonergic psychedelics are also well known to produce sympathomimetic effects.<ref name="Wsół2023">{{cite journal | vauthors = Wsół A | title = Cardiovascular safety of psychedelic medicine: current status and future directions | journal = Pharmacol Rep | volume = 75 | issue = 6 | pages = 1362–1380 | date = December 2023 | pmid = 37874530 | pmc = 10661823 | doi = 10.1007/s43440-023-00539-4 | url = }}</ref><ref name="NeumannDheinKirchhefer2024">{{cite journal | vauthors = Neumann J, Dhein S, Kirchhefer U, Hofmann B, Gergs U | title = Effects of hallucinogenic drugs on the human heart | journal = Front Pharmacol | volume = 15 | issue = | pages = 1334218 | date = 2024 | pmid = 38370480 | pmc = 10869618 | doi = 10.3389/fphar.2024.1334218 | doi-access = free | url = }}</ref><ref name="LeyHolzeArikci2023">{{cite journal | vauthors = Ley L, Holze F, Arikci D, Becker AM, Straumann I, Klaiber A, Coviello F, Dierbach S, Thomann J, Duthaler U, Luethi D, Varghese N, Eckert A, Liechti ME | title = Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants | journal = Neuropsychopharmacology | volume = 48 | issue = 11 | pages = 1659–1667 | date = October 2023 | pmid = 37231080 | pmc = 10517157 | doi = 10.1038/s41386-023-01607-2 | url = }}</ref>