Substituted phenethylamine

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), 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. 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.

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

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.

Cyclized phenethylamines

There are many cyclized phenethylamines. Examples include the following:

• Phenylalkylpyrrolidines like PEP, MPEP, prolintane, α-PPP, α-PVP, pyrovalerone, and MDPV
• Phenylalkylpiperidines like AC927 (phenethylpiperidine), diphenidine, fentanyl, and ifenprodil
• Tetrahydroisoquinolines (THIQs) 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 (2-AIs) like 2-aminoindane, MDAI, MMAI, DOM-AI, and Pyr-AI
• 2-Aminotetralins (2-ATs) like 2-aminotetralin, MDAT, DOM-AT, 8-OH-DPAT, and rotigotine
• 1-Aminomethylindanes (1-AMIs) like 2CB-Ind, AMMI, jimscaline, and bromojimscaline
• 3-Benzazepines like fenoldopam and lorcaserin
• Benzocyclobutenes (BCBs) like 2CBCB-NBOMe, S33005, TCB-2, tomscaline, and bromotomscaline
• Tetrahydrobenzopyranylamines like CT-5126
• Benzoxepins like TFMBOX
• 2-Benzylpiperidines and phenidates like 2-benzylpiperidine, methylphenidate, rimiterol, and DMBMPP
• Phenylcyclopropylamines like tranylcypromine, TMT, and DMCPA
• 3-Phenylpiperidines (3PIPs) like 3-phenylpiperidine, 3-PPP, OSU-6162 (PNU-96391), LPH-5, LPH-48, 2C-B-3PIP, 2C-B-3PIP-NBOMe, 2C-B-3PIP-POMe, and Z3517967757 (Z7757)
• 2-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 ergine (LSA) and LSD
• Partial ergolines and lysergamides like NDTDI, RU-27849, DEIMDHPCA, and DEMPDHPCA
• Pyridopyrroloquinoxalines like lumateperone, IHCH-7113, IHCH-7086, and ITI-1549
• Others like 6-AB, 2-ADN, 2C-B-PYR, 2C-B-5-hemiFLY-α6 (BNAP), 2CB7 (2C-B-5-hemiFLY-β7), 2CBecca, 2CJP, 2CLisaB, 2CLisaH, 2-naphthylamine, GYKI-52895, ivabradine, milnacipran, Org 6582, and ZC-B

Some additional cyclized phenethylamines have also been described.{{cite web | vauthors=Wolters RJ | title=Synthesis of Conformationally Constrained Analogs of Mescaline as Potential Psychotomimetics

Other related families that are not phenethylamines themselves include phenylpiperazines, benzylpiperazines, and 4-phenylpiperidines.

Notes

References

References

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