Substituted phenethylamine

Substituted phenethylamine
Substituted phenethylamine
Drug class
	The structural formula of phenethylamine with marked substitution points. Phenethylamine is obtained when; R2=R3=R4=R5=R6=RN=Rα=Rβ=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.

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.

Pharmacology

Many 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 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 MDMA (ecstasy), methamphetamine, and cathinone, are also members of the class. All of the substituted amphetamines and substituted methylenedioxyphenethylamines are substituted phenethylamines as well.

List of substituted phenethylamines

Selected Phenethylamines
Short Name	R^N	R^α	R^β	R²	R³	R⁴	R⁵	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	R²	R³	R⁴	R⁵	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.^[5]

Notes

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

References

^ 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. S2CID 211035606.
^ Wills B, Erickson T (2 February 2012). "Psychoactive Phenethylamine, Piperazine, and Pyrrolidinophenone Derivatives". Medical Toxicology of Drug Abuse: 156–192. doi:10.1002/9781118105955.ch10. ISBN 978-0-471-72760-6.
^ 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
^ 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. S2CID 208217863.
^ "Substituted Phenethylamine - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 27 August 2024.