Α-Methyltryptamine

Template:Short description Template:Cs1 config Template:Lowercase title Template:Infobox drug α-Methyltryptamine (αMT, AMT) is a psychedelic, stimulant, and entactogen drug of the tryptamine and α-alkyltryptamine families.<ref name="TiHKAL">Template:Cite web</ref><ref name="urlErowid AMT (alpha-methyltryptamine) Vault">Template:Cite web</ref> 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.<ref name="Barceloux2012">Template:Cite book</ref><ref name="Iversen2013">Template:Cite book</ref><ref name="AcademicPress2013">Template:Cite book</ref>

Side effects of αMT include agitation, restlessness, confusion, lethargy, pupil dilation, jaw clenching, and rapid heart rate, among others.<ref name="Barceloux2012" /><ref name="BolandAndolloHime2005" /> αMT acts as a releasing agent of serotonin, norepinephrine, and dopamine, as a serotonin receptor agonist, and as a weak monoamine oxidase inhibitor.<ref name="BloughLandavazo2014">Template:Cite journal</ref> αMT is a substituted tryptamine and is closely related to α-ethyltryptamine (αET) and other α-alkylated tryptamines.<ref name="BloughLandavazo2014" /><ref name="TiHKAL" />

αMT appears to have first been described by at least 1929.<ref name="GaddumHameed1954" /><ref name="Seki1929" /> It started being more studied in the late 1950s and was briefly used as an antidepressant in the Soviet Union in the 1960s.<ref name="Barceloux2012" /><ref name="ElliottBrandtFreeman2013" /><ref name="BolandAndolloHime2005" /><ref name="AraújoCarvalhoBastos2015" /><ref name="TittarelliMannocchiPantano2015" /> The drug started being used recreationally in the 1960s, with use increasing in the 1990s, and cases of death have been reported.<ref name="Barceloux2012" /><ref name="AraújoCarvalhoBastos2015" /><ref name="BolandAndolloHime2005" /><ref name="ElliottBrandtFreeman2013" /> αMT is a controlled substance in various countries, including the United States.<ref name="AraújoCarvalhoBastos2015" /><ref name="Barceloux2012" />

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Use and effects

Under the brand name Indopan or Indopane, αMT at doses of 5 to 10Template:Nbspmg was used for an antidepressant effect.<ref name="Barceloux2012" /><ref name="Iversen2013" /><ref name="AcademicPress2013" />

At a dose of 20 mg, it produces euphoria, while doses above 30 mg result in strong hallucinogenic effects. At doses over 30 mg, the compound may cause several side effects, including anxiety, muscle tightness, vomiting, and hyperthermia.<ref>Template:Cite journal</ref> A dose exceeding 40Template:Nbspmg is generally considered strong. In rare cases or extreme doses, the duration of effects might exceed 24Template:Nbsphours. Users report that αMT in freebase form is smoked, with doses between and 2 and 5Template:Nbspmg.<ref name="urlErowid AMT Vault : FAQ by Dialtonez">Template:Cite web</ref>Template:Unreliable source?<ref name="TiHKAL"/>

A dose of 20Template:Nbspmg of αMT is said to be equivalent to 50Template:Nbspμg of LSD.<ref name="BrimblecombePinder1975">Template:Cite book</ref> However, its onset of action is delayed, with effects appearing after only 3 to 4Template:Nbsphours, and it is longer-lasting.<ref name="BrimblecombePinder1975" /> In addition, αMT is described as unpleasant compared to LSD, with symptoms of nervousness, irritability, restlessness, and inability to relax.<ref name="BrimblecombePinder1975" /> It is also said to not have prominent visual effects.<ref name="BrimblecombePinder1975" />

Side effects

Neurologic side effects of αMT include agitation, restlessness, confusion, and lethargy.<ref name="Barceloux2012" /><ref name="BolandAndolloHime2005" /><ref name="BrimblecombePinder1975" /> Physical manifestations including vomiting, mydriasis (pupillary dilation), jaw clenching, tachycardia, salivation, diaphoresis (sweating), and elevations in blood pressure, temperature, and respiratory rate.<ref name="Barceloux2012" /><ref name="BolandAndolloHime2005">Template:Cite journal</ref>

Side effects self-reported by recreational users include anxiety, muscle tension, jaw tightness, pupil dilation, tachycardia, headaches, nausea, and vomiting, as well as psychedelic effects including visual hallucinations and an altered state of mind.<ref name="TiHKAL" /><ref name="urlErowid AMT Vault : Effects">Template:Cite web</ref>

αMT is capable of causing life-threatening side effects including hyperthermia, hypertension, and tachycardia.<ref name="BolandAndolloHime2005" /><ref name="Gillman2005">Template:Cite journal "drugs such as MDMA, ecstasy (3,4-methylenedioxymethamphetamine), if combined with MAOIs (including moclobemide) do also cause fatalities because they act as serotonin releasers"</ref> Fatalities have been reported in association with high doses or concomitant use of other drugs.<ref>Template:Cite news</ref>

Fatalities verified with toxicology and autopsy include those of a 22-year-old man in Miami-Dade County, Florida and a British teenager, both of whom died after consuming 1Template:Nbspg of αMT.<ref>Template:Cite news</ref><ref name="BolandAndolloHime2005" />

Interactions

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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">Template:Cite journal</ref> and as a non-selective serotonin receptor agonist.<ref name="pmid18057721">Template:Cite journal</ref> It has relatively weak psychedelic-like effects in animals compared to other psychedelic substituted tryptamines, for instance in terms of the head-twitch response in rodents.<ref name="BrimblecombePinder1975" />

Activities of αMT and related compounds
Compound	Monoamine release (Template:Abbrlink, nM)			5-HT_2A receptor agonism
Compound	Serotonin	Dopamine	Norepinephrine	Template:Abbrlink (nM)	E_max (%)
Tryptamine	33	164	716	7.4	104
Serotonin	44	>10,000	>10,000	Template:Abbr	Template:Abbr
N,N-DMT	114	>10,000	4,166	38	83
αMT	22–68	79–112	79–180	23	103
αET	23	232	640 (Template:Abbrlink = 78%)	>10,000	21
5-MeO-αMT	460	8,900	1,500	2.0–8.4	Template:Abbr
MDMA	57	376	77	Template:Abbr	Template:Abbr
Notes: The smaller the value, the more strongly the compound produces the effect. Refs:<ref name="GlennonDukat2023" /><ref name="BloughLandavazo2014" /><ref name="BloughLandavazoDecker2014">Template:Cite journal</ref><ref name="RothmanBaumann2003">Template:Cite journal</ref><ref name="NagaiNonakaSatohHisashiKamimura2007">Template:Cite journal</ref>

Monoamine oxidase inhibition

αMT has been shown as a reversible inhibitor of the enzyme monoamine oxidase (MAO) in vitro<ref>Template:Cite journal</ref> and in vivo.<ref>Template:Cite journal</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.Template:Refn Dextroamphetamine did not enhance the 5-hydroxytryptophan-induced rise of serotonin at any level.<ref name="GeyPletscher1961"/> The Template:Abbrlink of αMT for inhibition of MAO-A has been found to be 380Template:NbspnM.<ref name="WagmannBrandtKavanagh2017">Template:Cite journal</ref> This is similar to that of agents like para-methoxyamphetamine (PMA) and 4-methylthioamphetamine (4-MTA).<ref name="Reyes-ParadaIturriaga-VasquezCassels2019">Template:Cite journal</ref>

Serotonergic neurotoxicity

A close analogue of αMT, α-ethyltryptamine (αET), is known to be a serotonergic neurotoxin similarly to MDMA and para-chloroamphetamine (PCA).<ref name="Oeri2021">Template:Cite journal</ref><ref name="GlennonDukat2023">Template:Cite journal</ref><ref name="HuangJohnsonNichols1991">Template:Cite journal</ref>

Pharmacokinetics

2-Oxo-αMT, 6-hydroxy-αMT, 7-hydroxy-αMT, and 1′-hydroxy-αMT were detected as metabolites of αMT in male Wistar rats.<ref name="Barceloux2012" /><ref name="Szara1961">Template:Cite journal</ref><ref name="KanamoriKuwayamaTsujikawa2008">Template:Cite journal</ref>

Chemistry

αMT is a synthetic substituted tryptamine with a methyl substituent at the alpha carbon.<ref name="BloughLandavazo2014" /><ref name="BolandAndolloHime2005" /> This alpha substitution makes it a relatively poor substrate for monoamine oxidase A, thereby prolonging αMT's half-life, allowing it to reach the brain and enter the central nervous system. Its chemical relation to tryptamine is analogous to that of amphetamine to phenethylamine, amphetamine being α-methylphenethylamine.<ref name="BolandAndolloHime2005" /> αMT is closely related to the neurotransmitter serotonin (5-hydroxytryptamine) which partially explains its mechanism of action.

Synthesis

The chemical synthesis of αMT has been described.<ref name="TiHKAL" /> Its synthesis can be accomplished through several different routes, there's two "common" routes mainly via the Henry reaction aka Nitroadol condensation between indole-3-carboxaldehyde and nitroethane under amine salt or ionic liquid catalysis which produces 1-(3-indolyl)-2-nitropropene-1, 1-(3-indolyl)-2-nitropropene-1 can subsequently be reduced via a reducing agent such as lithium aluminum hydride<ref>Template:Cite web</ref> The alternative synthesis is the condensation between indole-3-acetone and hydroxylamine Template:Citation needed, followed by reduction of the obtained ketoxime with lithium aluminum hydride.<ref name="TiHKAL" />

Analogues

Many analogues of αMT are known, including α-ethyltryptamine (αET), 4-methyl-αMT, 5-chloro-αMT (PAL-542), 5-fluoro-αMT (PAL-544), 5-fluoro-αET (PAL-545), 5-methoxy-αMT (5-MeO-αMT), α,N-dimethyltryptamine (α,N-DMT; N-methyl-αMT), α,N,N-trimethyltryptamine (α,N,N-TMT; N-dimethyl-αMT), α-methylserotonin (α-methyl-5-HT; 5-hydroxy-αMT), and indolylpropylaminopentane (IPAP; α,N-dipropyltryptamine or α,N-DPT), among others.<ref name="BloughLandavazo2014" /><ref name="TiHKAL" /> Another analogue of αMT is the β-keto and N-methylated derivative BK-NM-AMT.<ref name="BloughDeckerLandavazo2019">Template:Cite journal</ref><ref name="US20240335414A1">Template:Cite patent</ref><ref name="WO2022061242A1">Template:Cite patent</ref>

α-Methyltryptophan, a prodrug of α-methylserotonin, also metabolizes into αMT, but only in small amounts.<ref name="Sourkes1991">Template:Cite journal</ref><ref name="RobergeMissalaSourkes1972">Template:Cite journal</ref><ref name="MarsdenCurzon1977">Template:Cite journal</ref>

There are seven possible positional isomers of aminopropylindole (API; IT), wherein the side chain is located at different positions of the indole ring system.<ref name="ScottPowerMcDermott2014">Template:Cite journal</ref><ref name="TiHKAL" /><ref name="BanksBauerBlough2014">Template:Cite journal</ref> These positional isomers include 1-API (α-methylisotryptamine; isoAMT; PAL-569), 2-API, 3-API (3-IT; α-methyltryptamine; AMT; PAL-17), 4-API, 5-API (5-IT; 3,4-pyrrolo[b]amphetamine; PAL-571), 6-API, and 7-API.<ref name="ScottPowerMcDermott2014" /><ref name="TiHKAL" /><ref name="BanksBauerBlough2014" /> 3-API or AMT is an α-alkyltryptamine, 1-API or isoAMT is an isotryptamine, and 4-API, 5-API, 6-API, and 7-API are all amphetamines.<ref name="ScottPowerMcDermott2014" /><ref name="TiHKAL" /><ref name="BanksBauerBlough2014" />

The analogue of AMT without the benzene part of the indole ring is 3-pyrrolylpropylamine.<ref name="GlennonChaurasiaTiteler1990">Template:Cite journal</ref>

History

αMT has been said to have been first synthesized in 1947, alongside α-ethyltryptamine (αET).<ref name="ElliottBrandtFreeman2013" /><ref name="GlennonDukat2023" /><ref name="SnyderKatz1947">Template:Cite journal</ref> However, other sources suggest that αMT was first described in the scientific literature by at least 1929.<ref name="GaddumHameed1954">Template:Cite journal</ref><ref name="Seki1929">Template:Cite journal</ref> It was specifically described as an antagonist of ergotamine at this time.<ref name="GaddumHameed1954" /><ref name="Seki1929" />

αMT started to be more intensively studied, along with αET, in the late 1950s and early 1960s.<ref name="ElliottBrandtFreeman2013" /><ref name="GreigWalkGibbons1959">Template:Cite journal</ref><ref name="HeinzelmanAnthonyLyttle1960">Template:Cite journal</ref><ref name="MurphreeDippyJenney1961">Template:Cite journal</ref><ref name="GeyPletscher1961">Template:Cite journal</ref><ref name="Himwich1961">Template:Cite journal</ref><ref name="VaneCollierCorne1961">Template:Cite journal</ref><ref name="KellerVigueraKundzins1962">Template:Cite journal</ref><ref name="SzaraHearstPutney1962">Template:Cite journal</ref><ref name="MashkovskiiTrubitsyna1963">Template:Cite journal</ref> It was researched by Upjohn (code name U-14,164E) and Sandoz (code name IT-290) as a possible pharmaceutical drug and was simultaneously marketed in the Soviet Union as an antidepressant under the brand name Indopan or Indopane in the 1960s.<ref name="AraújoCarvalhoBastos2015">Template:Cite journal</ref><ref name="TittarelliMannocchiPantano2015">Template:Cite journal</ref><ref name="BolandAndolloHime2005" /><ref name="US3296072">Template:Cite patent</ref> However, the drug was used clinically for only a short period of time before being withdrawn.<ref name="TittarelliMannocchiPantano2015" />

αMT started being used as a recreational drug in the 1960s<ref name="BolandAndolloHime2005" /> and use as a designer drug increased in the 1990s.<ref name="AraújoCarvalhoBastos2015" /> It became a controlled substance in the United States in 2003.<ref name="AraújoCarvalhoBastos2015" />

Society and culture

Names

αMT never received a formal generic name.<ref name="Elks2014">Template:Cite book</ref> In the scientific literature, it has been referred to as α-methyltryptamine or alpha-methyltryptamine (abbreviated as α-MT, αMT, or AMT).<ref name="AraújoCarvalhoBastos2015" /><ref name="TittarelliMannocchiPantano2015" /> αMT has also been referred to by developmental code names including IT-290 (Sandoz),<ref name="HollisterPrusmackPaulsen1960">Template:Cite journal</ref> NSC-97069,<ref name="ElliottBrandtFreeman2013">Template:Cite journal</ref> PAL-17,<ref name="BloughLandavazo2014" /> Ro 3-0926,<ref name="LessinLongParkes1966">Template:Cite journal</ref><ref name="LessinLongParkes1967">Template:Cite journal</ref> and U-14,164E (Upjohn).<ref name="BurninghamArimuraYunis1966">Template:Cite journal</ref><ref name="Offermeier1965">Template:Cite thesis</ref><ref name="ElliottBrandtFreeman2013" /><ref name="BolandAndolloHime2005" /> In the Soviet Union, the drug was merely referred to by its brand name Indopan or Indopane.<ref name="PubMed-Search-Indopan">Template:Cite web</ref><ref name="BolandAndolloHime2005" /> Other synonyms of αMT include 3-(2-aminopropyl)indole and 3-IT.<ref name="ElliottBrandtFreeman2013" /> (+)-αMT has been referred to by the code name IT-403.<ref name="ElliottBrandtFreeman2013" /><ref name="BolandAndolloHime2005" />

Legal status

Australia

The 5-methoxy analogue, 5-MeO-αMT is schedule 9 in Australia and αMT would be controlled as an analogue of this.<ref name="urlErowid 5-MeO-AMT Vault : Legal Status">Template:Cite web</ref>

Austria

αMT is placed under Austrian law (NPSG) Group 6.<ref name="who.int"/>

Canada

Canada has no mention of αMT in the Controlled Drugs and Substances Act.<ref name="urlCDSA List">Template:Cite web</ref>

China

As of October 2015 αMT is a controlled substance in China.<ref>Template:Cite web</ref>

Denmark

In Denmark (2010), the Danish Minister for the Interior and Health placed αMT to their lists of controlled substances (List B).<ref name="who.int">Template:Cite web</ref>

Finland

AMT, alfa-methyltryptamine, is a controlled drug in Finland.<ref>Template:Cite web</ref>

Germany

αMT is listed under the Narcotics Act in schedule 1 (narcotics not eligible for trade and medical prescriptions) in Germany.<ref name="who.int"/>

Hungary

αMT was controlled on the Schedule C list in Hungary in 2013.<ref name="who.int"/>

Lithuania

In Lithuania (2012), αMT is controlled as a tryptamine derivative put under control in the 1st list of Narcotic Drugs and Psychotropic Substances which use is prohibited for medical purposes.<ref name="who.int"/>

Slovakia

αMT was placed in 2013 on the List of Hazardous Substances in Annex, § 2 in Slovakia.<ref name="who.int"/>

Slovenia

αMT appeared on the Decree on Classification of Illicit Drugs in Slovenia (2013).<ref name="who.int"/>

Spain

αMT is legal in Spain.<ref>Template:Cite web</ref>

Sweden

Sveriges riksdags health ministry Statens folkhälsoinstitut classified αMT as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health) as of Mar 1, 2005, in their regulation SFS 2005:26 listed as alfa-metyltryptamin (AMT), making it illegal to sell or possess.<ref name='Swedenlaw'>Template:Citation</ref>

United Kingdom

αMT was made illegal in the United Kingdom as of 7 January 2015, along with 5-MeO-DALT.<ref>Template:Cite web</ref> This was following the events of 10 June 2014 when the Advisory Council on the Misuse of Drugs recommended that αMT be scheduled as a class A drug by updating the blanket ban clause on tryptamines.<ref name="ACMD tryptamines">Template:Cite web</ref>

United States

The Drug Enforcement Administration (DEA) placed αMT temporarily in schedule I of the Controlled Substances Act (CSA) on April 4, 2003, pursuant to the temporary scheduling provisions of the CSA (68 FR16427). On September 29, 2004, αMT was permanently controlled as a schedule I substance under the CSA (69FR 58050).<ref>Template:Cite news</ref>

Research

Besides depression, αMT has been studied in people with schizophrenia and other conditions.<ref name="BloughLandavazo2014" />

Notes

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References