Substituted phenethylamine explained

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.

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.

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 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.

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!ChemicalStructure! Short Name! R^N! R^α! R^β! R²! R³! R⁴! R⁵! Full Name! Biologic activity

									3-hydroxyphenethylamine	Trace amine
							OH		4-hydroxyphenethylamine	Trace amine
						OH	OH		3,4-dihydroxyphenethylamine	Catecholamine neurotransmitter
	Epinephrine (Adrenaline)			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
				OH		OH			β,3-dihydroxyphenethylamine	Trace amine
				OH			OH		β,4-dihydroxyphenethylamine	Trace aminergic α-adrenoceptor agonist
					OH		OH	OH	2,4,5-trihydroxyphenethylamine	neurotoxic agent for the dopamine and norepinephrine receptors
		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
		C(CH3)3		OH		CH2OH	OH		β,4-dihydroxy-3-hydroxymethyl-N-tert-butylphenethylamine	Short-action β2-adrenergic agonist
				CH3					β-methylphenethylamine	Stimulant
			CH3						α-methylphenethylamine	Monoamine releasing agent Stimulant
		CH3							N-methylphenethylamine	Trace amine endogenous amphetamine isomer
		(CH3)2							N,N-dimethylphenethylamine	Trivial effects (used as a food additive and flavoring agent)
		CH3	CH3						N-methylamphetamine; N,α-dimethylphenethylamine	Monoamine releasing agent stimulant; neurotoxin
			(CH3)2						α-methylamphetamine; α,α-dimethylphenethylamine	Stimulant, anorectic
			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
		-CH2-CH2-CH2-CH2-		C(OCH3)=O					N,α-butylene-β-methoxycarbonylphenethylamine	NDRI Stimulant
		CH3	CH3	OH					N-methyl-β-hydroxyamphetamine	Releasing agent stimulant; decongestant
			CH3	OH					d-β-hydroxyamphetamine	Moderately selective norepinephrine releasing agent
			CH3	=O					β-ketoamphetamine	Selective norepinephrine and dopamine releasing agent
		CH3	CH3	=O					N-methylcathinone	Selective norepinephrine and dopamine releasing agent
		CH3	CH3	=O			CH3		4-methylmethcathinone	Stimulant, unknown pharmacodynamic actions
		CH2CH3	CH3	=O					N-ethylcathinone	Stimulant and norepinephrine releasing agent
	Amfepramone (diethylpropion)	C2H5, C2H5^[3]	CH3	=O					N-diethyl-β-ketoamphetamine	Anorectic
		C(CH3)3	CH3	=O				Cl	5-chloro-N-tert-butyl-β-ketoamphetamine	NDRI
			CH3						3-trifluoromethyl-amphetamine	SSRA
		CH2CH3	CH3			CF3			3-trifluoromethyl-N-ethylamphetamine	SSRA
			CH3			-CH=CH-O-			5-(2-aminopropyl)benzofuran	Stimulant, entactogen
			CH3			-O-CH=CH-			6-(2-aminopropyl)benzofuran	Stimulant, entactogen
			CH3			-O-CH2-O-			3,4-methylenedioxy-amphetamine	Stimulant, psychedelic, entactogen
		CH2CH3	CH3			-O-CH2-O-			3,4-methylenedioxy-N-ethylamphetamine	Psychedelic, entactogen, and releasing agent
		CH3	CH3			-O-CH2-O-			3,4-methylenedioxy-N-methylamphetamine	Psychedelic, entactogen, and releasing agent
		CH3	CH3	=O		-O-CH2-O-			3,4-methylenedioxymethcathinone	Psychedelic, entactogen, and releasing agent
			CH3			-O-CH2-O-		OCH3	5-methoxy-3,4-methylenedioxy-amphetamine	Stimulant, psychedelic and entactogen
		CH3	CH3			-O-CH2-O-		OCH3	5-methoxy-3,4-methylenedioxy-N-methylamphetamine	Psychedelic, entactogen, and releasing agent
						-O-CH2-O-		OCH3	5-methoxy-3,4-methylenedioxyphenethylamine	Psychedelic and entactogen
							OCH3	OCH3	3,4,5-trimethoxyphenethylamine	Psychedelic and entactogen
						OCH3	OCH2CH2CH3	OCH3	2-(3,5-dimethoxy-4-propoxyphenyl)ethanamine	Psychedelic and entactogen
							OCH3	OCH3	2-(3-ethoxy-4,5-dimethoxyphenyl)ethanamine	Psychedelic and entactogen
						OCH3	OCH2CH1CH2	OCH3	4-Allyloxy-3,5-dimethyloxyphenylethylamine	Psychedelic and entactogen
						OCH3	OCH2C(CH2CH3)	OCH3	4-Methallyloxy-3,5-dimethoxyphenethylamine	Psychedelic and entactogen
						OCH2CH3	OCH2CH3	OCH3	3,4-Diethoxy-5-methoxyphenethylamine	Psychedelic and euphoriant
			CH3		OCH3		CH3	OCH3	2,5-dimethoxy-4-methylamphetamine	Psychedelic
			CH3		OCH3			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
					OCH3		Br	OCH3	2,5-dimethoxy-4-bromophenethylamine	Psychedelic, stimulant, entactogen and euphoriant
				=O	OCH3		Br	OCH3	2,5-dimethoxy-4-bromo-β-ketophenethylamine	Psychedelic, stimulant, entactogen and euphoriant
					OCH3		Cl	OCH3	2,5-dimethoxy-4-chlorophenethylamine	Psychedelic
					OCH3			OCH3	2,5-dimethoxy-4-fluorophenethylamine	Psychedelic
					OCH3		I	OCH3	2,5-dimethoxy-4-iodophenethylamine	Psychedelic, stimulant
					OCH3		CH3	OCH3	2,5-dimethoxy-4-methylphenethylamine	Psychedelic, stimulant
					OCH3		CH2-CH3	OCH3	2,5-dimethoxy-4-ethylphenethylamine	Psychedelic
					OCH3		CH2-CH3-CH3	OCH3	2,5-dimethoxy-4-propylphenethylamine	Entactogen, euphoriant and Psychedelic
					OCH3		NO2	OCH3	2,5-dimethoxy-4-nitrophenethylamine	euphoriant
					OCH3		S-CH2CH3	OCH3	2,5-dimethoxy-4-ethylthio-phenethylamine	Psychedelic
					OCH3			OCH3	2,5-dimethoxy-4-isopropylthio-phenethylamine	Psychedelic
					OCH3		S-CH2CH2CH3	OCH3	2,5-dimethoxy-4-propylthio-phenethylamine	Psychedelic
					OCH3			OCH3	2,5-dimethoxy-4-cyclopropylmethylthio-phenethylamine	Psychedelic
					OCH3		S-C(CH3)3	OCH3	2,5-dimethoxy-4-tert-butylthio-phenethylamine	Psychedelic
					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
		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
		CH2-C6H4-OCH3			OCH3		I	OCH3	2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine	Psychedelic
		CH2-C6H4-OCH3			OCH3		CH2	OCH3	2-(4-methyl-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine	Psychedelic
		CH2-C6H4-OCH3			OCH3		CH2-CH3	OCH3	2-(4-ethyl-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine	Psychedelic
		CH2-C6H4-OCH3			OCH3		CH2-CH3-CH3	OCH3	2-(4-propyl-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine	Psychedelic
		CH2-C6H4-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

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. https://www.sciencedirect.com/topics/medicine-and-dentistry/substituted-phenethylamine

See also

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

Notes and References

1. Inan . Funda . Brunt . Tibor M. . Contrucci . Ramon R. . Hondebrink . Laura . Franssen . Eric J. F. . 2020 . Novel Phenethylamines and Their Potential Interactions With Prescription Drugs: A Systematic Critical Review . Therapeutic Drug Monitoring . 42 . 2 . 271–281 . 10.1097/ftd.0000000000000725 . 32022784 . 211035606 . 0163-4356.
2. Wills . Brandon . Erickson . Timothy . 2012-02-02 . Psychoactive Phenethylamine, Piperazine, and Pyrrolidinophenone Derivatives . Medical Toxicology of Drug Abuse . 156–192 . 10.1002/9781118105955.ch10. 978-0-471-72760-6 .
3. Two ethyl groups attached to the amine group
4. Custodio. Raly James Perez. Sayson. Leandro Val. Botanas. Chrislean Jun. Abiero. Arvie. You. Kyung Yi. Kim. Mikyung. Lee. Hyun Jun. Yoo. Sung Yeun. Lee. Kun Won. Lee. Yong Sup. Seo. Joung-Wook. 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. 2019. 25. 6. en. e12850. 10.1111/adb.12850. 31749223. 208217863. 1369-1600.