Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative compounds of phenethylamine which can be formed by replacing, or substituting, one or more hydrogen atoms in the phenethylamine core structure with substituents. Phenylethylamines are also generally found to be central nervous system stimulants with many also being entactogens/empathogens, and hallucinogens.

Structural classification

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.

Pharmacology 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 DOM), entactogens (e.g., 3,4-methylenedioxy-N-methylamphetamine MDMA), 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. 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, however, the majority act through modulating monoamine transporter function, meanwhile the hallucinogens tend to have more direct interactions with post-synaptic receptors such as 5-HT2A while retaining some or most of their transporter modulating properties. The irreversible MAOIs that constitute a phenethylamine backbone, such as the phenethylamine and hydrazine derivative phenelzine, does not interact with any monoamine transporters or post-synaptic receptors but still elevates monoamine and trace amine concentrations by inhibiting monoamine oxidase enzymes.

Examples 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), mescaline, 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.

List of substituted phenethylamines

+ Selected Phenethylamines Structure Short Name RN Rα Rβ R2 R3 R4 R5 Full Name Biologic activity Phenethylamine phenethylamine Trace amine α,α-Dideuterophenethylamine D,D α,α-dideuterophenethylamine Deuterated drug α,α,β,β-Tetradeuterophenethylamine D,D D,D α,α,β,β-tetradeuterophenethylamine Deuterated drug para-Tyramine OH 4-hydroxyphenethylamine Trace amine Dopamine OH OH 3,4-dihydroxyphenethylamine Catecholamine neurotransmitter Epinephrine (Adrenaline) CH3 OH OH OH β,3,4-trihydroxy-N-methylphenethylamine Catecholamine neurotransmitter/Fight or Flight hormone Norepinephrine (Noradrenaline) OH OH OH β,3,4-trihydroxyphenethylamine Catecholamine neurotransmitter/Fight or Flight hormone Norfenefrine OH OH β,3-dihydroxyphenethylamine Trace amine para-Octopamine OH OH β,4-dihydroxyphenethylamine Trace aminergic α-adrenoceptor agonist Oxidopamine OH OH OH 2,4,5-trihydroxyphenethylamine neurotoxic agent for the dopamine and norepinephrine receptors Phenylephrine CH3 OH OH β,3-dihydroxy-N-methylphenethylamine α-adrenergic agonist; decongestantIsoprenalineCH(CH3)2OHOHOHβ,3-dihydroxy-N-isopropylphenethylamineβ-adrenergic agonist; decongestant Salbutamol C(CH3)3 OH CH2OH OH β,4-dihydroxy-3-hydroxymethyl-N-tert-butylphenethylamine Short-action β2-adrenergic agonist β-Methylphenethylamine CH3 β-methylphenethylamine Stimulant Amphetamine CH3 α-methylphenethylamine Monoamine releasing agent; Stimulant N-Methylphenethylamine CH3 N-methylphenethylamine Trace amine; endogenous amphetamine isomer (CH3)2 N,N-dimethylphenethylamine Trivial effects (used as a food additive and flavoring agent) Methamphetamine CH3 CH3 N-methylamphetamine; N,α-dimethylphenethylamine Monoamine releasing agent; stimulant; neurotoxin Phentermine (CH3)2 α-methylamphetamine; α,α-dimethylphenethylamine Stimulant, anorectic Ortetamine CH3 CH3 2-methylamphetamine; 2,α-dimethylphenethylamine Stimulant, anorecticPhenelzineNH2β-phenylethylhydrazineMonoamine oxidase inhibitorTranylcypromine -CH2-2-phenylcyclopropylamineMonoamine oxidase inhibitorSelegiline -CH2-C≡CHCH3N,α-dimethyl-N-2-propynylphenethylamineMAO-B selective monoamine oxidase inhibitor Methylphenidate -CH2-CH2-CH2-CH2- C(OCH3)=O N,α-butylene-β-methoxycarbonylphenethylamine NDRI; Stimulant Ephedrine / Pseudoephedrine CH3 CH3 OH N-methyl-β-hydroxyamphetamine Releasing agent; stimulant; decongestant Cathine CH3 OH d-β-hydroxyamphetamine Moderately selective norepinephrine releasing agent Cathinone CH3 =O β-ketoamphetamine Selective norepinephrine and dopamine releasing agent Methcathinone CH3 CH3 =O N-methylcathinone Selective norepinephrine and dopamine releasing agent Mephedrone CH3 CH3 =O CH3 4-methylmethcathinone Stimulant, unknown pharmacodynamic actions Ethcathinone CH2CH3 CH3 =O N-ethylcathinone Stimulant and norepinephrine releasing agent Amfepramone (diethylpropion) C2H5, C2H5Two ethyl groups attached to the amine group CH3 =O N-diethyl-β-ketoamphetamine Anorectic Bupropion C(CH3)3 CH3 =O Cl 5-chloro-N-tert-butyl-β-ketoamphetamine NDRI Norfenfluramine CH3 CF3 3-trifluoromethyl-amphetamine SSRA Fenfluramine CH2CH3 CH3 CF3 3-trifluoromethyl-N-ethylamphetamine SSRA 5-APB CH3 -CH=CH-O- 5-(2-aminopropyl)benzofuran Stimulant, entactogen 6-APB CH3 -O-CH=CH- 6-(2-aminopropyl)benzofuran Stimulant, entactogen MDA CH3 -O-CH2-O- 3,4-methylenedioxy-amphetamine Stimulant, psychedelic, entactogen MDEA CH2CH3 CH3 -O-CH2-O- 3,4-methylenedioxy-N-ethylamphetamine Psychedelic, entactogen, and releasing agent MDMA CH3 CH3 -O-CH2-O- 3,4-methylenedioxy-N-methylamphetamine Psychedelic, entactogen, and releasing agent MDMC (methylone) CH3 CH3 =O -O-CH2-O- 3,4-methylenedioxymethcathinone Psychedelic, entactogen, and releasing agent MMDA CH3 -O-CH2-O- OCH3 5-methoxy-3,4-methylenedioxy-amphetamine Stimulant, psychedelic and entactogen MMDMA CH3 CH3 -O-CH2-O- OCH3 5-methoxy-3,4-methylenedioxy-N-methylamphetamine Psychedelic, entactogen, and releasing agentLophophine -O-CH2-O- OCH3 5-methoxy-3,4-methylenedioxyphenethylamine Psychedelic and entactogen Mescaline OCH3 OCH3 OCH3 3,4,5-trimethoxyphenethylamine Psychedelic and entactogen Proscaline OCH3OCH2CH2CH3 OCH3 2-(3,5-dimethoxy-4-propoxyphenyl)ethanamine Psychedelic and entactogen Metaescaline OCH2CH3 OCH3 OCH3 2-(3-ethoxy-4,5-dimethoxyphenyl)ethanamine Psychedelic and entactogen Allylescaline OCH3OCH2CH1CH2 OCH3 4-Allyloxy-3,5-dimethyloxyphenylethylamine Psychedelic and entactogen Methallylescaline OCH3OCH2C(CH2CH3) OCH3 4-Methallyloxy-3,5-dimethoxyphenethylamine Psychedelic and entactogen Asymbescaline OCH2CH3OCH2CH3 OCH3 3,4-Diethoxy-5-methoxyphenethylaminePsychedelic and euphoriant DOM CH3 OCH3 CH3 OCH3 2,5-dimethoxy-4-methylamphetamine Psychedelic DOB CH3 OCH3 Br OCH3 2,5-dimethoxy-4-bromoamphetamine Psychedelic DOC CH3 OCH3 Cl OCH3 2,5-dimethoxy-4-chloroamphetamine Psychedelic DOI CH3 OCH3 I OCH3 2,5-dimethoxy-4-iodoamphetamine Psychedelic DON CH3 OCH3 NO2 OCH3 2,5-dimethoxy-4-nitroamphetamine Stimulant 2C-B OCH3 Br OCH3 2,5-dimethoxy-4-bromophenethylamine Psychedelic, stimulant, entactogen and euphoriant βk-2C-B =O OCH3 Br OCH3 2,5-dimethoxy-4-bromo-β-ketophenethylamine Psychedelic, stimulant, entactogen and euphoriant 2C-C OCH3 Cl OCH3 2,5-dimethoxy-4-chlorophenethylamine Psychedelic 2C-F OCH3 F OCH3 2,5-dimethoxy-4-fluorophenethylamine Psychedelic 2C-I OCH3 I OCH3 2,5-dimethoxy-4-iodophenethylamine Psychedelic, stimulant 2C-D OCH3 CH3 OCH3 2,5-dimethoxy-4-methylphenethylamine Psychedelic, stimulant 2C-E OCH3 CH2-CH3 OCH3 2,5-dimethoxy-4-ethylphenethylamine Psychedelic 2C-P OCH3 CH2-CH3-CH3 OCH3 2,5-dimethoxy-4-propylphenethylamine Entactogen, euphoriant and Psychedelic 2C-N OCH3 NO2 OCH3 2,5-dimethoxy-4-nitrophenethylamine euphoriant 2C-O-4 OCH3 (CH3)2CHO OCH3 2,5-Dimethoxy-4-propoxyphenethylamine Hallucinogen, psychedelic and entheogenic 2C-O-4 Entry in PiHKAL 2C-T-2 OCH3 S-CH2CH3 OCH3 2,5-dimethoxy-4-ethylthio-phenethylamine Psychedelic 2C-T-4 OCH3 S-CH(CH3)2 OCH3 2,5-dimethoxy-4-isopropylthio-phenethylamine Psychedelic 2C-T-7 OCH3 S-CH2CH2CH3 OCH3 2,5-dimethoxy-4-propylthio-phenethylamine Psychedelic 2C-T-8 OCH3 S-CH2-C3H5 OCH3 2,5-dimethoxy-4-cyclopropylmethylthio-phenethylamine Psychedelic 2C-T-19 OCH3 S-C(CH3)3 OCH3 2,5-dimethoxy-4-tert-butylthio-phenethylamine Psychedelic 2C-T-21 OCH3 S-CH2-CH2-F OCH3 2,5-dimethoxy-4-(2-fluoroethylthio)-phenethylamine Psychedelic and euphoriant 25B-NBOMeCH2-C6H4-OCH3 OCH3 Br OCH3 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine Psychedelic 25C-NBOMe CH2-C6H4-OCH3 OCH3 Cl OCH3 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine Psychedelic 25F-NBOMe CH2-C6H4-OCH3 OCH3 F OCH3 2-(4-fluoro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine Psychedelic 25I-NBOMe CH2-C6H4-OCH3 OCH3 I OCH3 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine Psychedelic 25D-NBOMe CH2-C6H4-OCH3 OCH3 CH2 OCH3 2-(4-methyl-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine Psychedelic 25E-NBOMe CH2-C6H4-OCH3 OCH3 CH2-CH3 OCH3 2-(4-ethyl-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine Psychedelic 25P-NBOMe CH2-C6H4-OCH3 OCH3 CH2-CH3-CH3 OCH3 2-(4-propyl-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine Psychedelic Mescaline-NBOMe CH2-C6H4-OCH3 OCH3 OCH3 OCH3 N-(2-Methoxybenzyl)-2-(3,4,5-trimethoxyphenyl)ethanamine Psychedelic25B-NBOH CH2–C6H4–OH OCH3 Br OCH3 N-(2-hydroxybenzyl)-2,5-dimethoxy-4-bromo-phenethylamine Psychedelic25C-NBOH CH2–C6H4–OH OCH3 Cl OCH3 N-(2-hydroxybenzyl)-2,5-dimethoxy-4-chloro-phenethylamine Psychedelic25I-NBOH CH2–C6H4–OH OCH3 I OCH3 N-(2-hydroxybenzyl)-2,5-dimethoxy-4-iodo-phenethylamine Psychedelic25I-NBF CH2–C6H4–F OCH3 I OCH3 N-(2-fluorobenzyl)-2,5-dimethoxy-4-iodo-phenethylamine Psychedelic Short Name RN Rα Rβ R2 R3 R4 R5 Full Name Biologic activity

Detection

MethodRequirementUV spectrometryReagent needed