Substituted phenethylamine

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The structural formula of any substituted phenethylamine contains a phenyl ring that is joined to an amino (NH) group via a two-carbon sidechain. Hence, any substituted phenethylamine can be classified according to the substitution of hydrogen (H) atoms on phenethylamine's phenyl ring, sidechain, or amino group with a specific group of atoms. Several classes of substances can be considered phenylethylamine derivatives such as Substituted amphetamines, where there is a methyl group substituted at the alpha position on the ethyl chain, Substituted methylenedioxyphenethylamines, where a methylenedioxy group is joined at the 3 and 4 positions on the phenyl ring, and Substituted cathinones, which have a carbonyl group substituted at the beta position on the ethyl chain, most of which also have a methyl group substituted at the alpha positioning making most cathinones substituted amphetamines as well.

Most substituted phenethylamines are psychoactive drugs which belong to a variety of different drug classes, including central nervous system stimulants (e.g., amphetamine), hallucinogens (e.g., 3,4,5-trimethoxyphenethylamine a.k.a. mescaline), 2,5-dimethoxy-4-methylamphetamine {{aka}} DOM), entactogen (e.g. MDA), appetite suppressants (e.g. phentermine), nasal decongestants and bronchodilators (e.g., levomethamphetamine and pseudoephedrine), antidepressants (e.g. bupropion and phenelzine), antiparkinson agents (e.g., selegiline), and vasopressors (e.g., ephedrine), among others.{{cite journal | vauthors = Inan F, Brunt TM, Contrucci RR, Hondebrink L, Franssen EJ | title = Novel Phenethylamines and Their Potential Interactions With Prescription Drugs: A Systematic Critical Review | journal = Therapeutic Drug Monitoring | volume = 42 | issue = 2 | pages = 271–281 | date = April 2020 | pmid = 32022784 | doi = 10.1097/ftd.0000000000000725 }}{{cite book | vauthors = Wills B, Erickson T | chapter = Psychoactive Phenethylamine, Piperazine, and Pyrrolidinophenone Derivatives | editor-last=Barceloux | editor-first=Donald G. | title=Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants | publisher=Wiley | date=9 March 2012 | isbn=978-0-471-72760-6 | doi=10.1002/9781118105955.ch10 | pages=156–192 }} Many of these psychoactive compounds exert their pharmacological effects primarily by modulating monoamine neurotransmitter systems; however, there is no known mechanism of action or biological target that is common to all members of this subclass.{{Medical citation needed|date=February 2016}}

Numerous endogenous compounds – including hormones, catecholamines such as dopamine and noradrenaline, and many trace amines (e.g. adrenaline, phenethylamine itself, tyramine, thyronamine, and iodothyronamine) – are substituted phenethylamines. Several notable recreational drugs, such as MDPV (Monkey Dust), MDMA (ecstasy), methamphetamine, and cathinone, are also members of the class. Many well-known prescription drugs are from the phenylethylamine class such as Adderall which uses Amphetamine, Desoxyn which uses methamphetamine, and Sudafed which uses pseudoephedrine.

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Detection of substituted phenethylamines, which include compounds such as 2C-B, MDMA, and other designer drugs, involves various analytical methods aimed at identifying these psychoactive substances. These compounds are structurally similar to amphetamines, making their detection challenging due to potential cross-reactivity in standard drug tests. Techniques like gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and immunoassay screenings are commonly employed for accurate identification. Advanced methods like high-performance liquid chromatography (HPLC) allow for precise separation and quantification of these substances even at low concentrations. Given the rising use of these drugs in recreational settings, developing sensitive and specific detection techniques remains crucial in forensic toxicology and clinical diagnostics.{{fact|date=December 2024}}

There are many cyclized phenethylamines. Examples include the following:

• Phenylalkylpyrrolidines like α-PVP, pyrovalerone, and prolintane
• Tetrahydroisoquinolines like anhalinine, pellotine, lophophorine, DOM-CR, nomifensine, tetrabenazine, and zelandopam
• Isoquinolines like perafensine, quinisocaine, and tilisolol
• Dihydroindoles and aminochromes like adrenochrome and adrenolutin
• 2-Aminoindanes like 2-aminoindane, MDAI, MMAI, and DOM-AI
• 2-Aminotetralins like 2-aminotetralin, MDAT, and DOM-AT
• 1-Aminomethylindanes like 2CB-Ind, AMMI, and jimscaline
• Benzazepines like fenoldopam
• Benzocyclobutenes like 2CBCB-NBOMe, S33005, TCB-2, and tomscaline
• Tetrahydrobenzopyranylamines like CT-5126
• Benzoxepins like BBOX, IBOX, and TFMBOX
• 2-Benzylpiperidines and phenidates like 2-benzylpiperidine and methylphenidate
• Phenylcyclopropylamines like tranylcypromine and DMCPA
• 3-Phenylpiperidines like OSU-6162 and LPH-5
• Phenylmorpholines like 2-phenylmorpholine, phenmetrazine, manifaxine, radafaxine, flumexadol, oxaflozane, and PF-219,061
• Phenyloxazolamines or aminorex analogues like aminorex and pemoline
• Tricyclic compounds like benzoctamine and dizocilpine
• Ergolines and lysergamides like LSD
• Partial ergolines and lysergamides like NDTDI, RU-27849, DEIMDHPCA, and DEMPDHPCA
• Others like 6-AB, 2-ADN, 2-naphthylamine, GYKI-52895, ivabradine, milnacipran, Org 6582, rimiterol, and ZC-B

Other cyclized phenethylamines have also been described.{{cite journal | vauthors = Nichols DE | title = Structure-activity relationships of phenethylamine hallucinogens | journal = J Pharm Sci | volume = 70 | issue = 8 | pages = 839–849 | date = August 1981 | pmid = 7031221 | doi = 10.1002/jps.2600700802 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=f57e387fb5be33822c05b7a3b90888ee717aad21}}{{cite journal | vauthors = Wolters RJ, Bej AJ, Tanner NS | title = Conformationally constrained analogs of mescaline | journal = J Pharm Sci | volume = 63 | issue = 9 | pages = 1379–1382 | date = September 1974 | pmid = 4427260 | doi = 10.1002/jps.2600630909 | url = }}{{cite web | vauthors=Wolters RJ | title=Synthesis of Conformationally Constrained Analogs of Mescaline as Potential Psychotomimetics

| website=ProQuest | url=https://www.proquest.com/openview/35dd826950b4c4799cbe838e814b0a2e/ | access-date=2 June 2025}}

Other related families include phenylpiperazines and benzylpiperazines.

• Substituted amphetamine
• Substituted methylenedioxyphenethylamine
• Substituted cathinone
• Substituted phenylmorpholine
• Substituted methoxyphenethylamine
• 2Cs, DOx, 4Cs, scalines, 3Cs, 25-NB, FLY
• Substituted tryptamine
• PiHKAL
• The Shulgin Index

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{{Phenethylamines}}

{{Chemical classes of psychoactive drugs}}

{{Monoamine releasing agents}}

{{Serotonin receptor modulators}}

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Category:Chemical classes of psychoactive drugs