Substituted phenethylamine

Substituted phenethylamine
Drug class
The structural formula of phenethylamine with marked substitution points. Phenethylamine is obtained when R^2=R^3=R^4=R^5=R^6=R^N=R^α=R^β=H.
Class identifiers
Chemical class	Substituted derivatives of phenethylamine
Legal status
In Wikidata

Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure;^{[note 1]} 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 structure of the parent phenethylamine

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 a.k.a. 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.^[1][2] 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]}

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), 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

Chemical Structure	Short Name	R^N	R^α	R^β	R^2	R^3	R^4	R^5	Full Name	Biologic activity
	meta-Tyramine					OH			3-hydroxyphenethylamine	Trace amine
	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; decongestant
	Isoprenaline	CH(CH3)2		OH		OH	OH		β,3-dihydroxy-N-isopropylphenethylamine	β-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
	N,N-Dimethylphenethylamine	(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, anorectic
	Phenelzine	NH2							β-phenylethylhydrazine	Monoamine oxidase inhibitor
	Tranylcypromine		-CH2-						2-phenylcyclopropylamine	Monoamine oxidase inhibitor
	Selegiline	-CH2-C≡CH	CH3						N,α-dimethyl-N-2-propynylphenethylamine	MAO-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, C2H5[note 2]	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	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 agent
	Lophophine					-O-CH2-O-		OCH3	5-methoxy-3,4-methylenedioxyphenethylamine	Psychedelic and entactogen
	Mescaline					OCH3	OCH3	OCH3	3,4,5-trimethoxyphenethylamine	Psychedelic and entactogen
	Proscaline					OCH3	OCH2CH2CH3	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					OCH3	OCH2CH1CH2	OCH3	4-Allyloxy-3,5-dimethyloxyphenylethylamine	Psychedelic and entactogen
	Methallylescaline					OCH3	OCH2C(CH2CH3)	OCH3	4-Methallyloxy-3,5-dimethoxyphenethylamine	Psychedelic and entactogen
	Asymbescaline					OCH2CH3	OCH2CH3	OCH3	3,4-Diethoxy-5-methoxyphenethylamine	Psychedelic 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[3]
	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-NBOMe[4]	CH2-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	Psychedelic
	25B-NBOH	CH2–C6H4–OH			OCH3		Br	OCH3	N-(2-hydroxybenzyl)-2,5-dimethoxy-4-bromo-phenethylamine	Psychedelic
	25C-NBOH	CH2–C6H4–OH			OCH3		Cl	OCH3	N-(2-hydroxybenzyl)-2,5-dimethoxy-4-chloro-phenethylamine	Psychedelic
	25I-NBOH	CH2–C6H4–OH			OCH3		I	OCH3	N-(2-hydroxybenzyl)-2,5-dimethoxy-4-iodo-phenethylamine	Psychedelic
	25I-NBF	CH2–C6H4–F			OCH3		I	OCH3	N-(2-fluorobenzyl)-2,5-dimethoxy-4-iodo-phenethylamine	Psychedelic
	Short Name	R^N	R^α	R^β	R^2	R^3	R^4	R^5	Full Name	Biologic activity

Detection

Method	Requirement
UV spectrometry	Reagent needed

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.^{[citation needed]}

See also

• Substituted amphetamine
• Substituted methylenedioxyphenethylamine
• Substituted cathinone
• Substituted phenylmorpholine
• 2Cs, DOx, 25-NB
• Substituted tryptamine
• PiHKAL
• The Shulgin Index

Notes

1. In other words, all of the compounds that belong to this class are structural analogs of phenethylamine.
2. Two ethyl groups attached to the amine group

References

1. Inan F, Brunt TM, Contrucci RR, Hondebrink L, Franssen EJ (April 2020). "Novel Phenethylamines and Their Potential Interactions With Prescription Drugs: A Systematic Critical Review". Therapeutic Drug Monitoring. 42 (2): 271–281. doi:10.1097/ftd.0000000000000725. PMID 32022784.
2. Wills B, Erickson T (2 February 2012). "Psychoactive Phenethylamine, Piperazine, and Pyrrolidinophenone Derivatives". Medical Toxicology of Drug Abuse. pp. 156–192. doi:10.1002/9781118105955.ch10. ISBN 978-0-471-72760-6.
3. Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. 2C-O-4 Entry in PiHKAL
4. Custodio RJ, Sayson LV, Botanas CJ, Abiero A, You KY, Kim M, et al. (November 2020). "25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential". Addiction Biology. 25 (6): e12850. doi:10.1111/adb.12850. PMID 31749223.