5-Fluoro-AMT

{{Short description|Psychedelic drug}} {{Infobox drug | Verifiedfields = verified | verifiedrevid = 477224287 | image = 5-Fluoro-AMT.svg | image_class = skin-invert-image | width = 225px | image2 = 5-Fluoro-AMT 3D.png | image_class2 = bg-transparent | width2 = 225px

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 712-08-3 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = P46235ZAP7 | PubChem = 12834 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 12304 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 96816 | synonyms = 5-Fluoro-α-methyltryptamine; 5-Fluoro-alpha-methyltryptamine; 5-Fluoro-αMT; 5-Fluoro-AMT; 5F-AMT; PAL-212; PAL-544

| IUPAC_name = 1-(5-fluoro-1''H''-indol-3-yl)propan-2-amine | C=11 | H=13 | F=1 | N=2 | SMILES = Fc1cc2c(cc1)[nH]cc2CC(N)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C11H13FN2/c1-7(13)4-8-6-14-11-3-2-9(12)5-10(8)11/h2-3,5-7,14H,4,13H2,1H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = CTGFDWBZMCPVED-UHFFFAOYSA-N }}

'''5-Fluoro-αMT''', also known as '''5-fluoro-α-methyltryptamine''' ('''5F-AMT''') or by its developmental code names '''PAL-212'''<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" /> and '''PAL-544''',<ref name="BanksBauerBlough2014">{{cite journal | vauthors = Banks ML, Bauer CT, Blough BE, Rothman RB, Partilla JS, Baumann MH, Negus SS | title = Abuse-related effects of dual dopamine/serotonin releasers with varying potency to release norepinephrine in male rats and rhesus monkeys | journal = Experimental and Clinical Psychopharmacology | volume = 22 | issue = 3 | pages = 274–284 | date = June 2014 | pmid = 24796848 | pmc = 4067459 | doi = 10.1037/a0036595 }}</ref><ref name="IsomerDesign">{{cite web | title=5-Fluoro-AMT | website=Isomer Design | date=11 November 2024 | url=https://isomerdesign.com/pihkal/explore/5104 | access-date=7 December 2024}}</ref> is a monoaminergic drug of the tryptamine and α-alkyltryptamine families related to α-methyltryptamine (αMT).<ref name="BloughLandavazoDecker2014" /><ref name="BloughLandavazoPartilla2014" /><ref name="BanksBauerBlough2014" /> It is taken orally.<ref name="McKennaTowers1984" /><ref name="ThisLandPress2013" />

The drug is known to act as a serotonin receptor agonist,<ref name="BloughLandavazoDecker2014" /><ref name="BloughLandavazoPartilla2014" /> monoamine releasing agent,<ref name="BloughLandavazoDecker2014" /><ref name="BloughLandavazoPartilla2014" /><ref name="BanksBauerBlough2014" /> and potent monoamine oxidase inhibitor.<ref name="Reyes-ParadaIturriaga-VasquezCassels2019" /><ref name="NakagawasaiAraiSatoh2004" /> It produces psychedelic- and stimulant-like effects in animals.<ref name="HalberstadtGeyer2018" /><ref name="NakagawasaiAraiSatoh2004"/><ref name="TadanoNedaHozumi1995" /><ref name="KalirSzara1963" /> 5-Fluoro-AMT is also known to be psychoactive in humans, though its effects have not been well-described.<ref name="McKennaTowers1984" /><ref name="ThisLandPress2013" />

5-Fluoro-AMT was first described in the scientific literature by 1963.<ref name="KalirSzara1963" /> There has been interest in 5-fluoro-AMT as a possible treatment for cocaine dependence.<ref name="BanksBauerBlough2014" />

==Use and effects== 5-Fluoro-AMT has been said to be psychoactive in humans at a dose of 25{{nbsp}}mg orally, although the qualitative nature of these effects has not been well-described.<ref name="McKennaTowers1984">{{cite journal | vauthors = McKenna DJ, Towers GH | title = Biochemistry and pharmacology of tryptamines and beta-carbolines. A minireview | journal = J Psychoactive Drugs | volume = 16 | issue = 4 | pages = 347–358 | date = 1984 | pmid = 6394730 | doi = 10.1080/02791072.1984.10472305 | url = https://bitnest.netfirms.com/external/10.1080/02791072.1984.10472305| url-access = subscription }}</ref><ref name="ThisLandPress2013" /> Preclinical studies suggest that 5-fluoro-αMT may be a psychedelic, stimulant, and/or entactogen in humans.<ref name="BloughLandavazoDecker2014" /><ref name="BloughLandavazoPartilla2014" /><ref name="BanksBauerBlough2014" /><ref name="HalberstadtGeyer2018" /><ref name="NakagawasaiAraiSatoh2004"/><ref name="TadanoNedaHozumi1995" /><ref name="KalirSzara1963" /> However, 5-fluoro-AMT may be dangerous in humans due to its concomitant potent monoamine oxidase inhibition.<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 = | article-number = 1590 | date = 2019 | pmid = 32038257 | pmc = 6989591 | doi = 10.3389/fphar.2019.01590 | doi-access = free | url = }}</ref><ref name="WagmannBrandtKavanagh2017" />

William Leonard Pickard has described his experiences with 5-fluoro-AMT, which he had synthesized along with 6-fluoro-AMT, in personal interviews.<ref name="ThisLandPress2013">{{cite web |title= Unusual Analogues: Drugs Used by Gordon Todd Skinner |url= http://thislandpress.com/2013/07/25/unusual-analogues-drugs-used-by-gordon-todd-skinner/ | archive-url=https://web.archive.org/web/20160417235026/http://thislandpress.com/2013/07/25/unusual-analogues-drugs-used-by-gordon-todd-skinner/ | archive-date =17 April 2016 | website= thislandpress.com |publisher=This Land Press |access-date=8 April 2016}}</ref> According to Pickard, 5-fluoro-AMT had a duration of at minimum 9{{nbsp}}hours and varied in length significantly.<ref name="ThisLandPress2013" /> The dose was 25{{nbsp}}mg and above.<ref name="ThisLandPress2013" /> Pickard has said that 5-fluoro-AMT was not a "warm drug" but that he remained favorable to it.<ref name="ThisLandPress2013" /> Its effects included time dilation among others.<ref name="ThisLandPress2013" /> He said that it gave him the worst post-trip headaches he'd experienced from any psychedelic and they lasted up to 24{{nbsp}}hours.<ref name="ThisLandPress2013" />

Pickard has said that 5-fluoro-AMT is less potent and long-lasting than 6-fluoro-AMT.<ref name="ThisLandPress2013" /> The related drug AMT was one of Pickard's favorite psychedelics, and he said that he took it more than 50{{nbsp}}times and experienced no negative side effects with it.<ref name="ThisLandPress2013" />

==Interactions== {{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

==Pharmacology== ===Pharmacodynamics=== 5-Fluoro-AMT has been found to act as a fairly balanced serotonin-norepinephrine-dopamine releasing agent (SNDRA),<ref name="BanksBauerBlough2014" /><ref name="BloughLandavazoDecker2014" /> as a serotonin 5-HT2A receptor agonist,<ref name="BloughLandavazoDecker2014" /><ref name="ChairungsrilerdFurukawaTadano1998">{{cite journal | vauthors = Chairungsrilerd N, Furukawa K, Tadano T, Kisara K, Ohizumi Y | title = Effect of gamma-mangostin through the inhibition of 5-hydroxy-tryptamine2A receptors in 5-fluoro-alpha-methyltryptamine-induced head-twitch responses of mice | journal = British Journal of Pharmacology | volume = 123 | issue = 5 | pages = 855–862 | date = March 1998 | pmid = 9535013 | pmc = 1565246 | doi = 10.1038/sj.bjp.0701695 }}</ref> and as a potent and specific MAO-A inhibitor.<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><ref>{{cite journal | vauthors = Kinemuchi H, Arai Y | title = Selective inhibition of monoamine oxidase A and B by two substrate-analogues, 5-fluoro-alpha-methyltryptamine and p-chloro-beta-methylphenethylamine | journal = Research Communications in Chemical Pathology and Pharmacology | volume = 54 | issue = 1 | pages = 125–8 | date = October 1986 | pmid = 3797802 | doi = 10.1016/0028-3908(91)90057-i | s2cid = 34761939 }}</ref><ref>{{cite journal | vauthors = Kim SK, Toyoshima Y, Arai Y, Kinemuchi H, Tadano T, Oyama K, Satoh N, Kisara K | display-authors = 6 | title = Inhibition of monoamine oxidase by two substrate-analogues, with different preferences for 5-hydroxytryptamine neurons | journal = Neuropharmacology | volume = 30 | issue = 4 | pages = 329–35 | date = April 1991 | pmid = 1852266 | doi = 10.1016/0028-3908(91)90057-i |s2cid = 34761939 }}</ref><ref>{{cite journal | vauthors = Corne SJ, Pickering RW | title = A possible correlation between drug-induced hallucinations in man and a behavioural response in mice | journal = Psychopharmacologia | volume = 11 | issue = 1 | pages = 65–78 | year = 1967 | pmid = 5302272 | doi = 10.1007/bf00401509 | s2cid = 3148623 }}</ref><ref>{{cite journal | vauthors = Yamamoto T, Ueki S | title = The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs | journal = Pharmacology, Biochemistry, and Behavior | volume = 14 | issue = 1 | pages = 89–95 | date = January 1981 | pmid = 6258178 | doi = 10.1016/0091-3057(81)90108-8 | s2cid = 45561708 }}</ref> Its {{Abbrlink|EC50|half-maximal effective concentration}} values in terms of monoamine release are 14 to 19{{nbsp}}nM for serotonin, 78 to 126{{nbsp}}nM for norepinephrine, and 32 to 37{{nbsp}}nM for dopamine in rat brain synaptosomes.<ref name="BanksBauerBlough2014" /><ref name="BloughLandavazoDecker2014" /><ref name="BloughLandavazoPartilla2014" /> The drug's {{Abbr|EC50|half-maximal effective concentration}} at the serotonin 5-HT2A receptor is 8.47{{nbsp}}nM and its {{Abbrlink|Emax|maximal efficacy}} at the receptor is 107%.<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> The {{Abbrlink|IC50|half-maximal inhibitory concentration}} of 5-fluoro-AMT for MAO-A is 180 to 450{{nbsp}}nM.<ref name="Reyes-ParadaIturriaga-VasquezCassels2019" /><ref name="NakagawasaiAraiSatoh2004">{{cite journal | vauthors = Nakagawasai O, Arai Y, Satoh SE, Satoh N, Neda M, Hozumi M, Oka R, Hiraga H, Tadano T | title = Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha-methylated substrate derivatives | journal = Neurotoxicology | volume = 25 | issue = 1–2 | pages = 223–232 | date = January 2004 | pmid = 14697897 | doi = 10.1016/S0161-813X(03)00101-3 | bibcode = 2004NeuTx..25..223N | url = }}</ref><ref name="WagmannBrandtKavanagh2017" /> This is similar to the potency of αMT, ''para''-methoxyamphetamine (PMA), and 4-methylthioamphetamine (4-MTA).<ref name="Reyes-ParadaIturriaga-VasquezCassels2019" />

5-Fluoro-αMT induces the head-twitch response, a behavioral proxy of psychedelic-like effects, in rodents.<ref name="HalberstadtGeyer2018">{{cite book | vauthors = Halberstadt AL, Geyer MA | title = Behavioral Neurobiology of Psychedelic Drugs | chapter = Effect of Hallucinogens on Unconditioned Behavior | series = Current Topics in Behavioral Neurosciences | volume = 36 | pages = 159–199 | date = 2018 | pmid = 28224459 | pmc = 5787039 | doi = 10.1007/7854_2016_466 | isbn = 978-3-662-55878-2 | chapter-url = }}</ref><ref name="NakagawasaiAraiSatoh2004"/><ref name="TadanoNedaHozumi1995">{{cite journal | vauthors = Tadano T, Neda M, Hozumi M, Yonezawa A, Arai Y, Fujita T, Kinemuchi H, Kisara K | title = alpha-Methylated tryptamine derivatives induce a 5-HT receptor-mediated head-twitch response in mice | journal = Neuropharmacology | volume = 34 | issue = 2 | pages = 229–234 | date = February 1995 | pmid = 7617148 | doi = 10.1016/0028-3908(94)00119-d | url = }}</ref> It is also known to reverse reserpine-induced behavioral depression, suggesting that it has antidepressant- or stimulant-like effects as well.<ref name="KalirSzara1963">{{cite journal | vauthors = Kalir A, Szara S | title = Synthesis and Pharmacological Activity of Fluorinated Tryptamine Derivatives | journal = J Med Chem | volume = 6 | issue = 6| pages = 716–719 | date = November 1963 | pmid = 14184932 | doi = 10.1021/jm00342a019 | url = https://bitnest.netfirms.com/external/10.1021/jm00342a019| url-access = subscription }}</ref> 5-Fluoro-AMT does not substitute for cocaine in drug discrimination tests but did substitute for cocaine in monkeys.<ref name="BanksBauerBlough2014" /> It does not facilitate intracranial self-stimulation (ICSS) in rodents.<ref name="BanksBauerBlough2014" />

==Chemistry== ===Analogues=== Analogues of 5-fluoro-AMT include 5-fluorotryptamine, 5-fluoro-DMT, 5-fluoro-AET, and BK-5F-NM-AMT, as well as 5-chloro-αMT, 6-fluoro-AMT, 7-chloro-AMT, 7-methyl-αET, 5-API (PAL-571), and flucindole, among others.

BK-5F-NM-AMT, the ''N''-methyl and β-keto derivative of 5-fluoro-AMT, is a serotonin–dopamine releasing agent (SDRA) analogously to 5-fluoro-AMT.<ref name="WO2022061242A1">{{cite patent | country = WO | number = 2022061242 | inventor = Baggott M | status = | title = Advantageous tryptamine compositions for mental disorders or enhancement | pubdate = 2023 March 24 | gdate = | fdate = 2021 September 20 | pridate = 2021 September 20 | assign1 = Tactogen | url = https://patents.google.com/patent/WO2022061242A1/}}</ref> In contrast to 5-fluoro-AMT and many other tryptamines however, BK-5F-NM-AMT is inactive as an agonist of serotonin receptors including the 5-HT1, 5-HT2, and 5-HT3 receptors and is inactive as a monoamine oxidase inhibitor (MAOI).<ref name="WO2022061242A1" />

==History== 5-Fluoro-AMT was first described in the scientific literature, by Asher Kalir and Stephen Szara, by 1963, and was described as showing antidepressant- or stimulant-like effects in rodents.<ref name="KalirSzara1963" /> It was first tried in humans by 1984.<ref name="McKennaTowers1984" /> The drug's psychedelic-like effects in animals were described by 1995.<ref name="TadanoNedaHozumi1995" /> 5-Fluoro-AMT's monoamine release and serotonin receptor agonism were shown by 2014, along with support for it having stimulant-like effects in monkeys.<ref name="BloughLandavazoDecker2014" /><ref name="BloughLandavazoPartilla2014" /><ref name="BanksBauerBlough2014" /> The drug was investigated as a possible candidate for treatment of cocaine dependence and these findings were published in 2014.<ref name="BanksBauerBlough2014" />

==Society and culture== ===Legal status=== ====Canada==== 5-Fluoro-AMT is not an explicitly nor implicitly controlled substance in Canada as of 2025.<ref name="CDSA2025">{{cite web | title=Controlled Drugs and Substances Act | website=Department of Justice Canada | date=5 December 2025 | url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html | access-date=20 January 2026}}</ref>

====United States==== 5-Fluoro-AMT is not an explicitly controlled substance in the United States.<ref name="OrangeBook2026">{{citation | title = Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026) | date = January 2026 | publisher = U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division | location = United States | url = https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf}}</ref> However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

==See also== * Substituted α-alkyltryptamine

==References== {{Reflist}}

==External links== * [https://isomerdesign.com/pihkal/explore/5104 5-Fluoro-AMT - Isomer Design]

{{Psychedelics}} {{Stimulants}} {{Navboxes | title = Pharmacodynamics | titlestyle = background:#ccccff | list1 = {{Serotonin receptor modulators}} {{Monoamine releasing agents}} {{Monoamine metabolism modulators}} }} {{Tryptamines}}

Category:5-HT2A agonists Category:Alpha-Alkyltryptamines Category:Entactogens Category:Fluoroarenes Category:5-Halotryptamines Category:Monoamine oxidase inhibitors Category:Psychedelic tryptamines Category:Serotonin-norepinephrine-dopamine releasing agents Category:Stimulants