Phenethylamine

Organic compound, a stimulant in humans

This article is about 2-phenylethylamine. For its isomer, see 1-phenylethylamine. For its derivatives, see substituted phenethylamine.

Pharmaceutical compound

Phenethylamine

Clinical data
Pronunciation| /fɛnˈɛθələmiːn/
Other names| Phenylethylamine; PEA; β-Phenylethylamine; β-Phenylethylamine; β-PEA; 2-Phenylethylamine; 2-PEA; Phetamine
Dependence
liability| Psychological: low–moderate[citation needed]
Physical: none
Addiction
liability| None–Low (w/o an MAO-B inhibitor)[1]
Moderate (with an MAO-B inhibitor)[1]
Routes of
administration| Oral (taken by mouth)
Drug class| Norepinephrine–dopamine releasing agent; Trace amine-associated receptor 1 (TAAR1) agonist; Psychostimulant; Sympathomimetic
ATC code|

* None

Physiological data
Source tissues| Substantia nigra pars compacta;
Ventral tegmental area;
Locus coeruleus;
many others
Target tissues| System-wide
Receptors| Varies greatly across species;
Human receptors: hTAAR1[2]
Precursor| L-Phenylalanine[3][4]
Biosynthesis| Aromatic L-amino acid decarboxylase (AADC)[3][4]
Metabolism| Primarily: MAO-B[3][4][5]
Other enzymes: MAO-A,[5][6] SSAOs (AOC2 & AOC3),[5][7] PNMT,[3][4][5] AANAT,[5] FMO3,[8][9] and others
Legal status
Legal status|

* AU: Unscheduled
* CA: Unscheduled
* NZ: Unscheduled
* UK: Unscheduled
* US: Unscheduled
* UN: Unscheduled

Pharmacokinetic data
Metabolism| Primarily: MAO-B[3][4][5]
Other enzymes: MAO-A,[5][6] SSAOs (AOC2 & AOC3),[5][7] PNMT,[3][4][5] AANAT,[5] FMO3,[8][9] and others
Elimination half-life|

* Exogenous: 5–10 minutes[10]
* Endogenous: ~30 seconds[3]

Excretion| Renal (kidneys)
Identifiers

IUPAC name

* 2-Phenylethan-1-amine

CAS Number|

* 64-04-0 Y

PubChem CID|

* 1001

IUPHAR/BPS|

* 2144

DrugBank|

* DB04325 Y

ChemSpider|

* 13856352 Y

UNII|

* 327C7L2BXQ

KEGG|

* C05332 Y

ChEBI|

* CHEBI:18397 Y

ChEMBL|

* ChEMBL610 Y

NIAID ChemDB|

* 018561

CompTox Dashboard (EPA)|

* DTXSID5058773

ECHA InfoCard| 100.000.523
Chemical and physical data
Formula| C8H11N
Molar mass| 121.183 g·mol−1
3D model (JSmol)|

* Interactive image

Density| 0.9640 g/cm3 [10]
Melting point| −60 °C (−76 °F) [10]
Boiling point| 195 °C (383 °F) [10]

SMILES

* NCCc1ccccc1

InChI

* InChI=1S/C8H11N/c9-7-6-8-4-2-1-3-5-8/h1-5H,6-7,9H2 Y

* Key:BHHGXPLMPWCGHP-UHFFFAOYSA-N Y

(verify)

Phenethylamine[note 1] (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons.[1][11][12] To a lesser extent, it also acts as a neurotransmitter in the human central nervous system.[13] In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation.[14] In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.

Phenethylamine is sold as a dietary supplement for purported mood and weight loss-related therapeutic benefits; however, in orally ingested phenethylamine, a significant amount is metabolized in the small intestine by monoamine oxidase B (MAO-B) and then aldehyde dehydrogenase (ALDH), which converts it to phenylacetic acid.[5] This means that for significant concentrations to reach the brain, the dosage must be higher than for other methods of administration.[5][6][15] Some authors have postulated that phenethylamine plays a role in affection without substantiating these claims with any direct evidence.[16][17]

Phenethylamines, or more properly, substituted phenethylamines, are the group of phenethylamine derivatives that contain phenethylamine as a "backbone"; in other words, this chemical class includes derivative compounds that are formed by replacing one or more hydrogen atoms in the phenethylamine core structure with substituents. The class of substituted phenethylamines includes all substituted amphetamines, and substituted methylenedioxyphenethylamines (MDxx), and contains many drugs which act as empathogens, stimulants, psychedelics, anorectics, bronchodilators, decongestants, and/or antidepressants, among others.

## Natural occurrence

[edit]

Phenethylamine is produced by a wide range of species throughout the plant and animal kingdoms, including humans;[14][18] it is also produced by certain fungi and bacteria (genera: Lactobacillus, Clostridium, Pseudomonas and the family Enterobacteriaceae) and acts as a potent antimicrobial against certain pathogenic strains of Escherichia coli (e.g., the O157:H7 strain) at sufficient concentrations.[19]

## Chemistry

[edit]

PEA powder and crystals

Phenethylamine is a primary amine, the amino-group being attached to a benzene ring through a two-carbon, or ethyl group.[10] It is a colourless liquid at room temperature that has a fishy odor, and is soluble in water, ethanol and ether.[10] Its density is 0.964 g/ml and its boiling point is 195 °C.[10] Upon exposure to air, it combines with carbon dioxide to form a solid carbonate salt.[20] Phenethylamine is strongly basic, pKb = 4.17 (or pKa = 9.83), as measured using the HCl salt, and forms a stable crystalline hydrochloride salt with a melting point of 217 °C.[10][21] Its experimental log P is 1.41.[10]

### Substituted derivatives

[edit]

Main article: Substituted phenethylamine

Substituted phenethylamines are a chemical class of organic compounds based upon the phenethylamine structure;[note 2] 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.

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., 2,5-dimethoxy-4-methylamphetamine), entactogens (e.g., 3,4-methylenedioxyamphetamine), appetite suppressants (e.g. phentermine), nasal decongestants and bronchodilators (e.g., pseudoephedrine), antidepressants (e.g. bupropion), 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 mechanism of action or biological target that is common to all members of this subclass.

Numerous endogenous compounds—including hormones, monoamine neurotransmitters, and many trace amines (e.g., dopamine, norepinephrine, adrenaline, tyramine, and others)—are substituted phenethylamines. Dopamine is simply phenethylamine with a hydroxyl group attached to the 3 and 4 position of the benzene ring. Several notable recreational drugs, such as MDMA (ecstasy), methamphetamine, and cathinones, are also members of the class. All of the substituted amphetamines are phenethylamines, as well.

Pharmaceutical drugs that are substituted phenethylamines include phenelzine, phenformin, and fanetizole, among many others.

The N-methylated derivative of phenethylamine is N-methylphenethylamine.

### Analogues

[edit]

Analogues of phenethylamine with the ethylamine side chain extended or shortened include phenylpropylamine and benzylamine. Another related analogue is phenylalaninol.

### Synthesis

[edit]

One method for preparing β-phenethylamine, set forth in J. C. Robinson and H. R. Snyder's Organic Syntheses (published 1955), involves the reduction of benzyl cyanide with hydrogen in liquid ammonia, in the presence of a Raney-Nickel catalyst, at a temperature of 130 °C and a pressure of 13.8 MPa. Alternative syntheses are outlined in the footnotes to this preparation.[22]

A much more convenient method for the synthesis of β-phenethylamine is the reduction of ω-nitrostyrene by lithium aluminium hydride in ether, whose successful execution was first reported by R. F. Nystrom and W. G. Brown in 1948.[23]

Phenethylamine can also be produced via the cathodic reduction of benzyl cyanide in a divided cell.[24]

Electrosynthesis of phenethylamine from benzyl cyanide[24]

Assembling phenethylamine structures for synthesis of compounds such as epinephrine, amphetamines, tyrosine, and dopamine by adding the beta-aminoethyl side chain to the phenyl ring is possible. This can be done via Friedel-Crafts acylation with N-protected acyl chlorides when the arene is activated, or by Heck reaction of the phenyl with N-vinyloxazolone, followed by hydrogenation, or by cross-coupling with beta-amino organozinc reagents, or reacting a brominated arene with beta-aminoethyl organolithium reagents, or by Suzuki cross-coupling.[25]

### Detection in body fluids

[edit]

Reviews that cover attention deficit hyperactivity disorder (ADHD) and phenethylamine indicate that several studies have found abnormally low urinary phenethylamine concentrations in ADHD individuals when compared with controls.[26] In treatment-responsive individuals, amphetamine and methylphenidate greatly increase urinary phenethylamine concentration.[26] An ADHD biomarker review also indicated that urinary phenethylamine levels could be a diagnostic biomarker for ADHD.[26]

Thirty minutes of moderate- to high-intensity physical exercise has been shown to induce an increase in urinary phenylacetic acid, the primary metabolite of phenethylamine.[3][27][28] Two reviews noted a study where the mean 24 hour urinary phenylacetic acid concentration following just 30 minutes of intense exercise rose 77% above its base level;[3][27][28] the reviews suggest that phenethylamine synthesis sharply increases during physical exercise during which it is rapidly metabolized due to its short half-life of roughly 30 seconds.[3][27][28][4] In a resting state, phenethylamine is synthesized in catecholamine neurons from L-phenylalanine by aromatic amino acid decarboxylase at approximately the same rate as dopamine is produced.[4] Monoamine oxidase deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone. Similarly, β-PEA would not be completely deaminated in the gut as it is a selective substrate for MAO-B, which is not primarily found in the gut. Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine, and serotonin, but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate.[14] Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life. Because of the pharmacological relationship between phenethylamine and amphetamine, the original paper and both reviews suggest that phenethylamine plays a prominent role in mediating the mood-enhancing euphoric effects of a runner's high, as both phenethylamine and amphetamine are potent euphoriants.[3][27][28]

Skydiving has also been shown to induce a marked increase in urinary phenethylamine concentrations.[10][29]

## Biological activity

[edit]

See also: Neurobiological effects of physical exercise § β-Phenylethylamine

Monoamine release of phenethylamine and related agents (EC50Tooltip Half maximal effective concentration, nM) Compound | NETooltip Norepinephrine | DATooltip Dopamine | 5-HTTooltip Serotonin | Ref

|
|
|
|

Phenethylamine | 10.9 | 39.5 | >10,000 | [30][31][32]
Tyramine | 40.6 | 119 | 2,775 | [33][32]
Tryptamine | 716 | 164 | 32.6 | [34][35]
Dextroamphetamine | 6.6–7.2 | 5.8–24.8 | 698–1,765 | [33][36]
Levoamphetamine | 9.5 | 27.7 | ND | [31][32]
Dextromethamphetamine | 12.3–13.8 | 8.5–24.5 | 736–1,292 | [33][37]
Levomethamphetamine | 28.5 | 416 | 4,640 | [33]
Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Refs: [38][39]

Phenethylamine pharmacodynamics in a TAAR1–dopamine neuron

* v
* t
* e

via AADC

Both amphetamine and phenethylamine induce neurotransmitter release from VMAT2[11][40][41] and bind to TAAR1.[12][42] When either binds to TAAR1, it reduces neuron firing rate and triggers protein kinase A (PKA) and protein kinase C (PKC) signaling, resulting in DAT phosphorylation.[12][42] Phosphorylated DAT then either operates in reverse or withdraws into the axon terminal and ceases transport.[12][42]

### Monoamine releasing agent

[edit]

Phenethylamine, being similar to amphetamine in its action at their common biomolecular targets, is a releasing agent of norepinephrine and dopamine.[11][12][42] It is roughly equipotent to amphetamine in this regard in vitro.[32] Phenethylamine is inactive as a psychostimulant under normal circumstances due to rapid metabolism by monoamine oxidase (MAO), but can become active in the presence of a monoamine oxidase inhibitor (MAOI).[32]

### TAAR1 agonist

[edit]

Phenethylamine is a potent agonist of the mouse, rat, and human trace amine-associated receptor 1 (TAAR1).[43][2] β-PEA is also an odorant binding TAAR4 in mice thought to mediate predator avoidance.[44] Similarly to the case of amphetamine, phenethylamine shows enhanced locomotor stimulation, a psychostimulant-like effect, in TAAR1 knockout mice.[45]

### Monoaminergic activity enhancer

[edit]

Phenethylamine is a monoaminergic activity enhancer (MAE) of serotonin, norepinephrine, and dopamine in addition to its catecholamine-releasing activity.[46][47][48] That is, it enhances the action potential-mediated release of these monoamine neurotransmitters.[46][47][48] The compound is active as a MAE at much lower concentrations than the concentrations at which it induces the release of catecholamines.[46][47][48] The MAE actions of phenethylamine and other MAEs may be mediated by TAAR1 agonism.[49][50] Synthetic and more potent MAEs like phenylpropylaminopentane (PPAP) and selegiline (L-deprenyl) have been derived from phenethylamine.[46][47]

### Other activities

[edit]

Unlike its derivatives norepinephrine (noradrenaline) and epinephrine (adrenaline), phenethylamine is inactive as an agonist of the α- and β-adrenergic receptors.[51]

### Effects in animals and humans

[edit]

According to Alexander Shulgin in PiHKAL, phenethylamine is completely inactive in humans at doses of up to 1,600 mg orally and 50 mg intravenously.[52] This can be attributed to its extremely rapid metabolic breakdown rather than pharmacodynamic inactivity.[52]

Although exogenous phenethylamine on its own is inactive, its metabolism can be strongly inhibited and it can thereby become active, showing psychostimulant effects, when combined with a monoamine oxidase inhibitor (MAOI), specifically monoamine oxidase B (MAO-B) inhibitors like selegiline.[53][54] Oral L-phenylalanine (a precursor of phenethylamine) and/or phenethylamine itself in combination with selegiline has been studied in the treatment of depression and has been reported to be effective.[46][55][56][57][58] Misuse of phenethylamine in combination with selegiline has also been reported.[59][60]

The LD50Tooltip median lethal dose values of phenethylamine include 175 mg/kg i.p. in mice, 320 mg/kg s.c. in mice, 100 mg/kg i.v. in mice, 100 mg/kg parenterally in mice, 39 mg/kg intracervically in mice, and 200 mg/kg i.p. in guinea pigs.[10] Its LDLo values include 800 mg/kg p.o. in rats, 100 mg/kg i.p. in rats, 450 μg/kg s.c. in rats, and 300 mg/kg via an unspecified route in mice.[10]

## Pharmacokinetics

[edit]

Biosynthetic pathways for catecholamines and trace amines in the human brain[61][62][63]

L-Phenylalanine

L-Tyrosine

L-DOPA

Epinephrine

Phenethylamine

p-Tyramine

Dopamine

Norepinephrine

N-Methylphenethylamine

N-Methyltyramine

p-Octopamine

Synephrine

3-Methoxytyramine

AADC

AADC

AADC

primary
pathway

PNMT

PNMT

PNMT

PNMT

AAAH

AAAH

brain
CYP2D6

minor
pathway

COMT

DBH

DBH

In humans, catecholamines and phenethylaminergic trace amines are derived from the amino acid L-phenylalanine.

By oral route, phenethylamine's half-life is 5–10 minutes;[10] endogenously produced PEA in catecholamine neurons has a half-life of roughly 30 seconds.[3] In humans, PEA is metabolized by phenylethanolamine N-methyltransferase (PNMT),[3][4][5][64] monoamine oxidase A (MAO-A),[5][6] monoamine oxidase B (MAO-B),[3][4][5][15] the semicarbazide-sensitive amine oxidases (SSAOs) AOC2 and AOC3,[5][7] flavin-containing monooxygenase 3 (FMO3),[8][9] and aralkylamine N-acetyltransferase (AANAT).[5][65] N-Methylphenethylamine, an isomer of amphetamine, is produced in humans via the metabolism of phenethylamine by PNMT.[3][4][64] β-Phenylacetic acid is the primary urinary metabolite of phenethylamine and is produced via monoamine oxidase metabolism and subsequent aldehyde dehydrogenase metabolism.[5] Phenylacetaldehyde is the intermediate product which is produced by monoamine oxidase and then further metabolized into β-phenylacetic acid by aldehyde dehydrogenase.[5][66]

When the initial phenylethylamine concentration in the brain is low, brain levels can be increased 1000-fold when taking a monoamine oxidase inhibitor (MAOI), particularly a MAO-B inhibitor, and by 3–4 times when the initial concentration is high.[67]

## Legality

[edit]

Phenylethylamine is not a scheduled substance in the United States. However, at least one person in the United States has been prosecuted under the federal analogue act for selling Phenylethylamine with the prosecutions argument that PEA is a structural analog of Amphetamine and Methamphetamine.[68][69][70]

## Notes

[edit]

1. ^ Synonyms and alternate spellings include: phenylethylamine, β-phenylethylamine (β-PEA), 2-phenylethylamine, 1-amino-2-phenylethane, and 2-phenylethan-1-amine.
2. ^ In other words, all of the compounds that belong to this class are structural analogs of phenethylamine.

## References

[edit]

1. ^ a b c Pei Y, Asif-Malik A, Canales JJ (April 2016). "Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications". Frontiers in Neuroscience. 10: 148. doi:10.3389/fnins.2016.00148. PMC 4820462. PMID 27092049. "Furthermore, evidence has accrued on the ability of TAs to modulate brain reward (i.e., the subjective experience of pleasure) and reinforcement (i.e., the strengthening of a conditioned response by a given stimulus; Greenshaw, 2021), suggesting the involvement of the TAs in the neurological adaptations underlying drug addiction, a chronic relapsing syndrome characterized by compulsive drug taking, inability to control drug intake and dysphoria when access to the drug is prevented (Koob, 2009). Consistent with its hypothesized role as "endogenous amphetamine," β-PEA was shown to possess reinforcing properties, a defining feature that underlies the abuse liability of amphetamine and other psychomotor stimulants. β-PEA was also as effective as amphetamine in its ability to produce conditioned place preference (i.e., the process by which an organism learns an association between drug effects and a particular place or context) in rats (Gilbert and Cooper, 1983) and was readily self-administered by dogs that had a stable history (i.e., consisting of early acquisition and later maintenance) of amphetamine or cocaine self-administration (Risner and Jones, 1977; Shannon and Thompson, 1984). In another study, high concentrations of β-PEA dose-dependently maintained responding in monkeys that were previously trained to self-administer cocaine, and pretreatment with a MAO-B inhibitor, which delayed β-PEA deactivation, further increased response rates (Bergman et al., 2001)."
2. ^ a b Khan MZ, Nawaz W (October 2016). "The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system". Biomedicine & Pharmacotherapy. 83: 439–449\. doi:10.1016/j.biopha.2016.07.002. PMID 27424325.
3. ^ a b c d e f g h i j k l m Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends in Pharmacological Sciences. 26 (5): 274–281\. doi:10.1016/j.tips.2005.03.007. PMID 15860375. "The pharmacology of TAs might also contribute to a molecular understanding of the well-recognized antidepressant effect of physical exercise [51]. In addition to the various beneficial effects for brain function mainly attributed to an upregulation of peptide growth factors [52,53], exercise induces a rapidly enhanced excretion of the main β-PEA metabolite β-phenylacetic acid (b-PAA) by on average 77%, compared with resting control subjects [54], which mirrors increased β-PEA synthesis in view of its limited endogenous pool half-life of ~30 s [18,55]."
4. ^ a b c d e f g h i Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacology & Therapeutics. 125 (3): 363–375\. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186. "Trace amines are metabolized in the mammalian body via monoamine oxidase"
5. ^ a b c d e f g h i j k l m n Wishart DS, Guo AC, Oler E, Wang F, Anjum A, Peters H, et al. "Showing metabocard for Phenylethylamine (HMDB0012275)". Human Metabolome Database, HMDB. 5.0.
6. ^ a b c Suzuki O, Katsumata Y, Oya M (March 1981). "Oxidation of beta-phenylethylamine by both types of monoamine oxidase: examination of enzymes in brain and liver mitochondria of eight species". Journal of Neurochemistry. 36 (3): 1298–1301\. doi:10.1111/j.1471-4159.1981.tb01734.x. PMID 7205271. S2CID 36099388.
7. ^ a b Kaitaniemi S, Elovaara H, Grön K, Kidron H, Liukkonen J, Salminen T, et al. (August 2009). "The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase". Cellular and Molecular Life Sciences. 66 (16): 2743–2757\. doi:10.1007/s00018-009-0076-5. PMC 11115939. PMID 19588076. S2CID 30090890. "The preferred in vitro substrates of AOC2 were found to be 2-phenylethylamine, tryptamine and p-tyramine instead of methylamine and benzylamine, the favored substrates of AOC3."
8. ^ a b Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacology & Therapeutics. 106 (3): 357–387\. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. "The biogenic amines, phenethylamine and tyramine, are N-oxygenated by FMO to produce the N-hydroxy metabolite, followed by a rapid second oxygenation to produce the trans-oximes (Lin & Cashman, 1997a, 1997b). This stereoselective N-oxygenation to the trans-oxime is also seen in the FMO-dependent N-oxygenation of amphetamine (Cashman et al., 1999) ... Interestingly, FMO2, which very efficiently N-oxygenates N-dodecylamine, is a poor catalyst of phenethylamine N-oxygenation. The most efficient human FMO in phenethylamine N-oxygenation is FMO3, the major FMO present in adult human liver; the Km is between 90 and 200 μM (Lin & Cashman, 1997b)."
9. ^ a b Robinson-Cohen C, Newitt R, Shen DD, Rettie AE, Kestenbaum BR, Himmelfarb J, et al. (August 2016). "Association of FMO3 Variants and Trimethylamine N-Oxide Concentration, Disease Progression, and Mortality in CKD Patients". PLOS ONE. 11 (8): e0161074. Bibcode:2016PLoSO..1161074R. doi:10.1371/journal.pone.0161074. PMC 4981377. PMID 27513517. "TMAO is generated from trimethylamine (TMA) via metabolism by hepatic flavin-containing monooxygenase isoform 3 (FMO3). ... FMO3 catalyzes the oxidation of catecholamine or catecholamine-releasing vasopressors, including tyramine, phenylethylamine, adrenaline, and noradrenaline [32, 33]."
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24. ^ a b Krishnan V, Muthukumaran A, Udupa HV (1979). "The electroreduction of benzyl cyanide on iron and cobalt cathodes". Journal of Applied Electrochemistry. 9 (5): 657–659\. doi:10.1007/BF00610957. S2CID 96102382.
25. ^ Molander GA, Vargas F (January 2007). "Beta-aminoethyltrifluoroborates: efficient aminoethylations via Suzuki-Miyaura cross-coupling". Organic Letters. 9 (2): 203–206\. doi:10.1021/ol062610v. PMC 2593899. PMID 17217265.
26. ^ a b c Scassellati C, Bonvicini C, Faraone SV, Gennarelli M (October 2012). "Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses". Journal of the American Academy of Child and Adolescent Psychiatry. 51 (10): 1003–1019.e20. doi:10.1016/j.jaac.2012.08.015. PMID 23021477. "Although we did not find a sufficient number of studies suitable for a meta-analysis of PEA and ADHD, three studies20,57,58 confirmed that urinary levels of PEA were significantly lower in patients with ADHD compared with controls. ... Administration of D-amphetamine and methylphenidate resulted in a markedly increased urinary excretion of PEA,20,60 suggesting that ADHD treatments normalize PEA levels. ... Similarly, urinary biogenic trace amine PEA levels could be a biomarker for the diagnosis of ADHD,20,57,58 for treatment efficacy,20,60 and associated with symptoms of inattentivenesss.59 ... With regard to zinc supplementation, a placebo controlled trial reported that doses up to 30 mg/day of zinc were safe for at least 8 weeks, but the clinical effect was equivocal except for the finding of a 37% reduction in amphetamine optimal dose with 30 mg per day of zinc.110"
27. ^ a b c d Szabo A, Billett E, Turner J (October 2001). "Phenylethylamine, a possible link to the antidepressant effects of exercise?". British Journal of Sports Medicine. 35 (5): 342–343\. doi:10.1136/bjsm.35.5.342. PMC 1724404. PMID 11579070. "The 24 hour mean urinary concentration of phenylacetic acid was increased by 77% after exercise. ... These results show substantial increases in urinary phenylacetic acid levels 24 hours after moderate to high intensity aerobic exercise. As phenylacetic acid reflects phenylethylamine levels3, and the latter has antidepressant effects, the antidepressant effects of exercise appear to be linked to increased phenylethylamine concentrations. Furthermore, considering the structural and pharmacological analogy between amphetamines and phenylethylamine, it is conceivable that phenylethylamine plays a role in the commonly reported "runners high" thought to be linked to cerebral β-endorphin activity. The substantial increase in phenylacetic acid excretion in this study implies that phenylethylamine levels are affected by exercise. ... A 30 minute bout of moderate to high intensity aerobic exercise increases phenylacetic acid levels in healthy regularly exercising men. The findings may be linked to the antidepressant effects of exercise."
28. ^ a b c d Berry MD (January 2007). "The potential of trace amines and their receptors for treating neurological and psychiatric diseases". Reviews on Recent Clinical Trials. 2 (1): 3–19\. CiteSeerX 10.1.1.329.563. doi:10.2174/157488707779318107. PMID 18473983. "It has also been suggested that the antidepressant effects of exercise are due to an exercise-induced elevation of PE [151]."
29. ^ Paulos MA, Tessel RE (February 1982). "Excretion of beta-phenethylamine is elevated in humans after profound stress". Science. 215 (4536): 1127–1129\. Bibcode:1982Sci...215.1127P. doi:10.1126/science.7063846. PMID 7063846. "The urinary excretion rate of the endogenous, amphetamine-like substance beta-phenethylamine was markedly elevated in human subjects in association with an initial parachuting experience. The increases were delayed in most subjects and were not correlated with changes in urinary pH or creatinine excretion."
30. ^ Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, et al. (February 2015). "Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter". Drug and Alcohol Dependence. 147: 1–19\. doi:10.1016/j.drugalcdep.2014.12.005. PMC 4297708. PMID 25548026.
31. ^ a b Forsyth AN (22 May 2012). "Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines". ScholarWorks@UNO. Retrieved 4 November 2024.
32. ^ a b c d e Blough B (July 2008). "Dopamine-releasing agents" (PDF). In Trudell ML, Izenwasser S (eds.). Dopamine Transporters: Chemistry, Biology and Pharmacology. Hoboken [NJ]: Wiley. pp. 305–320\. ISBN 978-0-470-11790-3. OCLC 181862653. OL 18589888W.
33. ^ a b c d Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, et al. (January 2001). "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin". Synapse. 39 (1): 32–41\. doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3. PMID 11071707.
34. ^ Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (October 2014). "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology. 231 (21): 4135–4144\. doi:10.1007/s00213-014-3557-7. PMC 4194234. PMID 24800892.
35. ^ Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters. 24 (19): 4754–4758\. doi:10.1016/j.bmcl.2014.07.062. PMC 4211607. PMID 25193229.
36. ^ Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, et al. (2013). "Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products". Neuropsychopharmacology. 38 (4): 552–562\. doi:10.1038/npp.2012.204. PMC 3572453. PMID 23072836.
37. ^ Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, et al. (2012). "The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue". Neuropsychopharmacology. 37 (5): 1192–1203\. doi:10.1038/npp.2011.304. PMC 3306880. PMID 22169943.
38. ^ Rothman RB, Baumann MH (October 2003). "Monoamine transporters and psychostimulant drugs". Eur J Pharmacol. 479 (1–3): 23–40\. doi:10.1016/j.ejphar.2003.08.054. PMID 14612135.1–3&rft.pages=23-40&rft.date=2003-10&rft_id=info:doi/10.1016/j.ejphar.2003.08.054&rft_id=info:pmid/14612135&rft.aulast=Rothman&rft.aufirst=RB&rft.au=Baumann,+MH&rfr_id=info:sid/en.wikipedia.org:Phenethylamine" class="Z3988">
39. ^ Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry. 6 (17): 1845–1859\. doi:10.2174/156802606778249766. PMID 17017961.
40. ^ Erickson JD, Schafer MK, Bonner TI, Eiden LE, Weihe E (May 1996). "Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter". Proceedings of the National Academy of Sciences of the United States of America. 93 (10): 5166–5171\. Bibcode:1996PNAS...93.5166E. doi:10.1073/pnas.93.10.5166. PMC 39426. PMID 8643547.
41. ^ Offermanns, S, Rosenthal, W, eds. (2008). Encyclopedia of Molecular Pharmacology (2nd ed.). Berlin: Springer. pp. 1219–1222\. ISBN 978-3540389163.
42. ^ a b c d Gozal EA, O'Neill BE, Sawchuk MA, Zhu H, Halder M, Chou CC, et al. (2014). "Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord". Frontiers in Neural Circuits. 8: 134. doi:10.3389/fncir.2014.00134. PMC 4224135. PMID 25426030. "TAAR1 activity appears to depress monoamine transport and limit dopaminergic and serotonergic neuronal firing rates via interactions with presynaptic D2 and 5-HT1A autoreceptors, respectively (Wolinsky et al., 2007; Lindemann et al., 2008; Xie and Miller, 2008; Xie et al., 2008; Bradaia et al., 2009; Revel et al., 2011; Leo et al., 2014).  ... TAAR1 and TAAR4 labeling in all neurons appeared intracellular, consistent with previous reported results for TAAR1 (Miller, 2011). A cytoplasmic location of ligand and receptor (e.g., tyramine and TAAR1) supports intracellular activation of signal transduction pathways, as suggested previously (Miller, 2011). ... Additionally, once transported intracellularly, they could act on presynaptic TAARs to alter basal activity (Miller, 2011). ... As reported for TAAR1 in HEK cells (Bunzow et al., 2001; Miller, 2011), we observed cytoplasmic labeling for TAAR1 and TAAR4, both of which are activated by the TAs (Borowsky et al., 2001). A cytoplasmic location of the ligand and the receptor (e.g., tyramine and TAAR1) would support intracellular activation of signal transduction pathways (Miller, 2011). Such a co-localization would not require release from vesicles and could explain why the TAs do not appear to be found there (Berry, 2004; Burchett and Hicks, 2006)."
43. ^ Gainetdinov RR, Hoener MC, Berry MD (July 2018). "Trace Amines and Their Receptors". Pharmacol Rev. 70 (3): 549–620\. doi:10.1124/pr.117.015305. PMID 29941461.
44. ^ Liberles SD (October 2015). "Trace amine-associated receptors: ligands, neural circuits, and behaviors". Current Opinion in Neurobiology. 34: 1–7\. doi:10.1016/j.conb.2015.01.001. PMC 4508243. PMID 25616211.
45. ^ Wolinsky TD, Swanson CJ, Smith KE, Zhong H, Borowsky B, Seeman P, et al. (October 2007). "The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia". Genes Brain Behav. 6 (7): 628–639\. doi:10.1111/j.1601-183X.2006.00292.x. PMID 17212650. "Most notably, Caron & Gainetdinov (personal communication) have recently observed that group-housed TA1 KO mice show enhanced sensitivity to the locomotor stimulating effects of both amphetamine and β-PEA relative to group-housed WT littermates, as well as normal habituation to an open field."
46. ^ a b c d e Shimazu S, Miklya I (May 2004). "Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 28 (3): 421–427\. doi:10.1016/j.pnpbp.2003.11.016. PMID 15093948. S2CID 37564231.
47. ^ a b c d Knoll J (August 2003). "Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives". Neurochem Res. 28 (8): 1275–1297\. doi:10.1023/a:1024224311289. PMID 12834268.
48. ^ a b c Knoll J, Miklya I, Knoll B, Markó R, Rácz D (1996). "Phenylethylamine and tyramine are mixed-acting sympathomimetic amines in the brain". Life Sci. 58 (23): 2101–2114\. doi:10.1016/0024-3205(96)00204-4. PMID 8649195.
49. ^ Harsing LG, Knoll J, Miklya I (August 2022). "Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum". Int J Mol Sci. 23 (15): 8543. doi:10.3390/ijms23158543. PMC 9369307. PMID 35955676.
50. ^ Harsing LG, Timar J, Miklya I (August 2023). "Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline". Int J Mol Sci. 24 (17): 13334. doi:10.3390/ijms241713334. PMC 10487936. PMID 37686140.
51. ^ Pinckaers NE, Blankesteijn WM, Mircheva A, Shi X, Opperhuizen A, Schooten FV, et al. (May 2024). "In Vitro Activation of Human Adrenergic Receptors and Trace Amine-Associated Receptor 1 by Phenethylamine Analogues Present in Food Supplements". Nutrients. 16 (11): 1567. doi:10.3390/nu16111567. PMC 11174489. PMID 38892500.
52. ^ a b "#142 - Phenethylamine". Isomer Design. Retrieved 10 November 2024.
53. ^ Yasar S, Goldberg JP, Goldberg SR (1 January 1996). "Are metabolites of l-deprenyl (Selegiline) useful or harmful? Indications from preclinical research". Deprenyl — Past and Future. Journal of Neural Transmission. Supplementum. Vol. 48\. pp. 61–73\. doi:10.1007/978-3-7091-7494-4_6. ISBN 978-3-211-82891-5. PMID 8988462.
54. ^ Heinonen EH, Lammintausta R (1991). "A review of the pharmacology of selegiline". Acta Neurologica Scandinavica. Supplementum. 136: 44–59\. doi:10.1111/j.1600-0404.1991.tb05020.x. PMID 1686954.
55. ^ Janssen PA, Leysen JE, Megens AA, Awouters FH (September 1999). "Does phenylethylamine act as an endogenous amphetamine in some patients?". Int J Neuropsychopharmacol. 2 (3): 229–240\. doi:10.1017/S1461145799001522. PMID 11281991.
56. ^ Birkmayer W, Riederer P, Linauer W, Knoll J (1984). "L-deprenyl plus L-phenylalanine in the treatment of depression". J Neural Transm. 59 (1): 81–87\. doi:10.1007/BF01249880. PMID 6425455.
57. ^ Sabelli HC (March 1991). "Rapid treatment of depression with selegiline-phenylalanine combination". J Clin Psychiatry. 52 (3): 137. PMID 1900832.
58. ^ Sabelli H, Fink P, Fawcett J, Tom C (1996). "Sustained antidepressant effect of PEA replacement". J Neuropsychiatry Clin Neurosci. 8 (2): 168–71\. doi:10.1176/jnp.8.2.168. PMID 9081552.
59. ^ McKean AJ, Leung JG, Dare FY, Sola CL, Schak KM (2015). "The Perils of Illegitimate Online Pharmacies: Substance-Induced Panic Attacks and Mood Instability Associated With Selegiline and Phenylethylamine". Psychosomatics. 56 (5): 583–587\. doi:10.1016/j.psym.2015.05.003. PMID 26198572.
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## External links

[edit]

* Phenethylamine MS Spectrum
* PEA (phenethylamine) - isomer design (PiHKAL entry)

* v
* t
* e

Chocolate

Cocoa bean|

* Chocolate liquor
* Cocoa butter
* Cocoa solids
* Theobroma cacao
* Types

Components|

* Anandamide
* Caffeine
* Endorphins
* Enkephalin
* Flavan-3-ol
* Lecithin
* Phenethylamine
* Phenylalanine
* Salsolinol
* Tetramethylpyrazine
* Theobromine
* Theophylline
* Tryptamine
* Tryptophan
* Tyramine
* Tyrosine
* Valeric acid

Types|

* Baking
* Compound
* Couverture
* Dark
* Gianduja
* Milk
* Organic
* Raw
* Ruby
* White

Products|

* Beverages
* Caffè mocha
* Milk
* Hot chocolate
* Liqueur
* Biscuit
* Brownie
* Cake
* Chocolate bar
* Brands
* Chocolate chip
* Chocolate chip cookie
* Chocolate-covered foods
* Chocolate crackles
* Chocolate crinkle
* Cioccolato di Modica
* Coins
* Fudge
* Ganache
* Gravy
* Ice cream
* Mole
* Pudding
* Spread
* Syrup
* Truffle

Processes|

* Aeration
* Broma process
* Conching
* Dutch process
* Enrober
* Sugar crust
* Tempering

Industry|

* Bean-to-bar
* Manufacturers
* Chocolaterie
* Chocolatier
* Côte d'Ivoire–Ghana Cocoa Initiative
* Environmental impact
* Fair trade cocoa
* Child labour in cocoa production
* Harkin–Engel Protocol
* International Cocoa Organization
* International Cocoa Quarantine Centre
* Production by country
* Ghana
* Ghana Cocoa Board
* Ivory Coast
* Nigeria
* São Tomé and Príncipe
* Sri Lanka
* World Cocoa Foundation

By country|

* Belgium
* France
* Switzerland

Other topics|

* Chocolate bloom
* Chocolate fountain
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* Chocolatiers
* Cocoa smuggling
* History
* In savory cooking
* Military chocolate
* Switzerland
* United States

* Category
* Outline
* Glossary

* v
* t
* e

Amphetamine

Main articles
and
pharmaceuticals|

| Amphetamine|

* Adzenys ER
* Adzenys XR-ODT
* Dyanavel XR
* Evekeo
* Evekeo ODT
* Mixed amphetamine salts
* Adderall
* Adderall XR
* Mydayis

|

Levoamphetamine|

N/A

Dextroamphetamine|

* Dexedrine
* ProCentra
* Zenzedi

Lisdexamfetamine|

* Vyvanse

Neuropharmacology|

| Biomolecular targets|

* TAAR1 (full agonist)
* CART (mRNATooltip messenger RNA inducer)
* 5-HT1A receptor (low affinity ligand)
* MAO (weak competitive inhibitor)
* Carbonic anhydrases hCA4, hCA5A, hCA5B, hCA7, hCA12, hCA13, and hCA14 (enzyme activator)

|

Inhibited transporters|

* DAT
* NET
* SERT
* VMAT1
* VMAT2
* EAAT3
* SLC22A3
* SLC22A5

Active metabolites|

* 4-Hydroxyamphetamine
* 4-Hydroxynorephedrine
* Norephedrine

Related articles|

* ADHD
* ADHD management
* Amphetamine psychosis
* Benzedrine in popular culture
* Dopamine
* Doping in sport
* Executive functions
* Formetorex
* ΔFosB
* History and culture of substituted amphetamines
* Methamphetamine
* Methylphenidate
* N-Methylphenethylamine
* Motivational salience
* Incentive salience
* Narcolepsy
* Neurobiological effects of physical exercise § Attention deficit hyperactivity disorder
* Nootropic
* Norepinephrine
* Obesity
* Performance-enhancing substance
* Phenethylamine
* Phentermine
* Phenylacetone
* Recreational drug use
* Serotonin
* Substituted amphetamine
* Trace amine

* Category

* v
* t
* e

Neurotransmitters

Amino acid-derived|

| Major excitatory /
inhibitory systems|

| Glutamate system|

* Agmatine
* Aspartic acid (aspartate)
* Glutamic acid (glutamate)
* Glutathione
* Glycine
* GSNO
* GSSG
* Kynurenic acid
* NAA
* NAAG
* Proline
* Serine

|

GABA system|

* GABA
* GABOB
* GHB

Glycine system|

* α-Alanine
* β-Alanine
* Glycine
* Hypotaurine
* Proline
* Sarcosine
* Serine
* Taurine

GHB system|

* GHB
* T-HCA (GHC)

Biogenic amines|

| Monoamines|

* 6-OHM
* Dopamine
* Epinephrine (adrenaline)
* NAS (normelatonin)
* Norepinephrine (noradrenaline)
* Serotonin (5-HT)

|

Trace amines|

* 3-Iodothyronamine
* N-Methylphenethylamine
* N-Methyltryptamine
* m-Octopamine
* p-Octopamine
* Phenylethanolamine
* Phenethylamine
* Synephrine
* Tryptamine
* m-Tyramine
* p-Tyramine

Others|

* Histamine

Neuropeptides|

* See here instead.

Lipid-derived|

| Endocannabinoids|

* 2-AG
* 2-AGE (noladin ether)
* 2-ALPI
* 2-OG
* AA-5-HT
* Anandamide (AEA)
* DEA
* LPI
* NADA
* NAGly
* OEA
* Oleamide
* PEA
* RVD-Hpα
* SEA
* Virodhamine (O-AEA)

|

Neurosteroids|

* See here instead.

Nucleobase-derived|

| Nucleosides|

| Adenosine system|

* ADP
* AMP
* ATP

|

Vitamin-derived|

|

Miscellaneous|

| Cholinergic system|

* Acetylcholine

|

Gasotransmitters|

* Carbon monoxide (CO)
* Hydrogen sulfide (H2S)
* Nitric oxide (NO)

|

Candidates|

* Acetaldehyde
* Ammonia (NH3)
* Carbonyl sulfide (COS)
* Nitrous oxide (N2O)
* Sulfur dioxide (SO2)

|

* v
* t
* e

Monoamine releasing agents

DRAsTooltip Dopamine releasing agents|

* Morpholines: Fenbutrazate
* Fenmetramide
* Morazone
* Morforex
* Phendimetrazine
* Phenmetrazine
* Pseudophenmetrazine

* Oxazolines: 4-MAR
* Aminorex
* Clominorex
* Cyclazodone
* Fenozolone
* Fluminorex
* Pemoline
* Thozalinone

* Phenethylamines: 2-OH-PEA
* 4-CAB
* 4-FA
* 4-FMA
* 4-MA
* 4-MMA
* Alfetamine
* Amfecloral
* Amfepentorex
* Amfepramone
* Amphetamine (Dextroamphetamine
* Levoamphetamine)
* Amphetaminil
* β-Me-PEA
* BDB
* BOH
* Benzphetamine
* Buphedrone
* Butylone
* Cathine
* Cathinone
* Clobenzorex
* Clortermine
* D-Deprenyl
* DMA
* DMMA
* Dimethylamphetamine
* Ephedrine
* Ethcathinone
* EBDB
* Ethylone
* Etilamfetamine
* Famprofazone
* Fenethylline
* Fenproporex
* Flephedrone
* Fludorex
* Furfenorex
* Hordenine
* 4-Hydroxyamphetamine
* Iofetamine (123I)
* Lisdexamfetamine
* Lophophine
* Mefenorex
* Mephedrone
* Metamfepramone
* Methamphetamine
* Dextromethamphetamine
* Levomethamphetamine
* Methcathinone
* Methedrone
* MMDA
* MMDMA
* MBDB
* MDA (tenamfetamine)
* MDEA
* MDMA (midomafetamine)
* MDMPEA
* MDOH
* MDPEA
* Methylone
* Morforex
* Ortetamine
* pBA
* pCA
* pIA
* Pholedrine
* Phenethylamine
* Pholedrine
* Phenpromethamine
* Prenylamine
* Propylamphetamine
* Pseudoephedrine
* Tiflorex
* Tyramine
* Xylopropamine
* Zylofuramine

* Piperazines: 2C-B-BZP
* BZP
* MBZP
* MDBZP
* MeOPP
* oMPP

* Others: 2-ADN
* 2-AI
* 2-AT
* 4-BP
* 5-APDI
* 5-IAI
* Amineptine
* Clofenciclan
* Cyclopentamine
* Cypenamine
* Cyprodenate
* Feprosidnine
* Gilutensin
* Heptaminol
* Hexacyclonate
* Indanorex
* Isometheptene
* Methylhexanamine
* Naphthylaminopropane
* Octodrine
* Phthalimidopropiophenone
* Phenylbiguanide
* Propylhexedrine

NRAsTooltip Norepinephrine releasing agents|

* Morpholines: Fenbutrazate
* Fenmetramide
* Morazone
* Morforex
* Phendimetrazine
* Phenmetrazine
* Pseudophenmetrazine

* Oxazolines: 4-MAR
* Aminorex
* Clominorex
* Cyclazodone
* Fenozolone
* Fluminorex
* Pemoline
* Thozalinone

* Phenethylamines: 2-OH-PEA
* 4-CAB
* 4-FA
* 4-FMA
* 4-MA
* 4-MMA
* Alfetamine
* Amfecloral
* Amfepentorex
* Amfepramone
* Amphetamine
* Dextroamphetamine
* Levoamphetamine
* Amphetaminil
* β-Me-PEA
* BDB
* Benzphetamine
* BOH
* Buphedrone
* Butylone
* Cathine
* Cathinone
* Clobenzorex
* Clortermine
* Dimethylamphetamine
* DMA
* DMMA
* EBDB
* Ephedrine
* Ethcathinone
* Ethylone
* Etilamfetamine
* Famprofazone
* Fenethylline
* Fenproporex
* Flephedrone
* Fludorex
* Furfenorex
* Hordenine
* 4-Hydroxyamphetamine
* 5-APDI (IAP)
* Iofetamine (123I)
* Lisdexamfetamine
* Lophophine
* MBDB
* MDA (tenamfetamine)
* MDEA
* MDMA (midomafetamine)
* Metamfepramone
* MDMPEA
* MDOH
* MDPEA
* Mefenorex
* Mephedrone
* Mephentermine
* Methamphetamine
* Dextromethamphetamine
* Levomethamphetamine
* Methcathinone
* Methedrone
* Methylone
* Morforex
* Naphthylaminopropane
* Ortetamine
* pBA
* pCA
* Pentorex
* Phenethylamine
* Pholedrine
* Phenpromethamine
* Phentermine
* Phenylpropanolamine
* pIA
* Prenylamine
* Propylamphetamine
* Pseudoephedrine
* Selegiline (also D-Deprenyl)
* Tiflorex
* Tyramine
* Xylopropamine
* Zylofuramine

* Piperazines: 2C-B-BZP
* BZP
* MBZP
* mCPP
* MDBZP
* MeOPP
* oMPP
* pFPP

* Others: 2-ADN
* 2-AI
* 2-AT
* 2-BP
* 4-BP
* 5-IAI
* Clofenciclan
* Cyclopentamine
* Cypenamine
* Cyprodenate
* Feprosidnine
* Gilutensin
* Heptaminol
* Hexacyclonate
* Indanorex
* Isometheptene
* Methylhexanamine
* Octodrine
* Phthalimidopropiophenone
* Propylhexedrine
* Tuaminoheptane

SRAsTooltip Serotonin releasing agents|

* Aminoindanes: 5-IAI
* AMMI
* ETAI
* MDAI
* MDMAI
* MMAI
* TAI

* Aminotetralins: 6-CAT
* 8-OH-DPAT
* MDAT
* MDMAT

* Oxazolines: 4-Methylaminorex
* Aminorex
* Clominorex
* Fluminorex

* Phenethylamines: 2-Methyl-MDA
* 4-CAB
* 4-FA
* 4-FMA
* 4-HA
* 4-MTA
* 5-APDB
* 5-Methyl-MDA
* 6-APDB
* 6-Methyl-MDA
* AEMMA
* Amiflamine
* BDB
* BOH
* Brephedrone
* Butylone
* Chlorphentermine
* Cloforex
* Amfepramone
* Metamfepramone
* DCA
* Dexfenfluramine
* DFMDA
* DMA
* DMMA
* EBDB
* EDMA
* Ethylone
* Etolorex
* Fenfluramine
* Flephedrone
* Flucetorex
* IAP
* Iofetamine
* Levofenfluramine
* Lophophine
* MBDB
* MDA (tenamfetamine)
* MDEA
* MDHMA
* MDMA (midomafetamine)
* MDMPEA
* MDOH
* MDPEA
* Mephedrone
* Methedrone
* Methylone
* MMA
* MMDA
* MMDMA
* MMMA
* NAP
* Norfenfluramine
* 4-TFMA
* pBA
* pCA
* pIA
* PMA
* PMEA
* PMMA
* TAP

* Piperazines: 2C-B-BZP
* 3-MeOPP
* BZP
* DCPP
* MBZP
* mCPP
* MDBZP
* MeOPP
* Mepiprazole
* oMPP
* pCPP
* pFPP
* pTFMPP
* TFMPP

* Tryptamines: 4-Methyl-αET
* 4-Methyl-αMT
* 5-CT
* 5-MeO-αET
* 5-MeO-αMT
* 5-MT
* αET
* αMT
* DMT
* Tryptamine

* Others: Indeloxazine
* Viqualine

Others|

* DAT modulators: Agonist-like: SoRI-9804
* SoRI-20040; Antagonist-like: SoRI-20041

* Adrenergic release blockers: Bethanidine
* Bretylium
* Guanadrel
* Guanazodine
* Guanethidine
* Guanoxan

See also: Receptor/signaling modulators • Monoamine reuptake inhibitors • Adrenergics • Dopaminergics • Serotonergics • Monoamine metabolism modulators • Monoamine neurotoxins

* v
* t
* e

Monoaminergic activity enhancers

Endogenous|

* Phenylethylamine (PEA)
* Tryptamine
* Tyramine

Synthetic|

* 4-Fluorodeprenyl
* Amphetamine
* Dextroamphetamine
* Levoamphetamine
* Benzofuranylpropylaminopentane (BPAP)
* Deprenyl
* D-Deprenyl
* Selegiline (L-deprenyl)
* Desmethylselegiline (DMS)
* Indolylpropylaminopentane (IPAP)
* Methamphetamine
* Dextromethamphetamine
* Levomethamphetamine
* Methylenedioxyphenylpropylaminopentane (MPAP)
* Naphthylpropylaminopentane (NPAP)
* Phenylpropylaminopentane (PPAP)

Antagonists|

* 3-F-BPAP
* EPPTB
* Rasagiline

See also: Receptor/signaling modulators • Monoamine releasing agents • Monoamine reuptake inhibitors • Monoamine metabolism modulators • TAAR ligands

* v
* t
* e

Trace amine-associated receptor modulators

TAAR1Tooltip Trace amine-associated receptor 1|

| Agonists|

| Endogenous|

* Monoamine neurotransmitters
* Dopamine
* Histamine
* Epinephrine (adrenaline)
* Norepinephrine (noradrenaline)
* Serotonin
* Trace amines
* 3-Iodothyronamine
* 3-Methoxytyramine
* N-Methylphenethylamine
* N-Methyltyramine
* m-Octopamine
* p-Octopamine
* β-Phenethylamine
* Phenylethanolamine
* Synephrine
* Tryptamine
* m-Tyramine
* p-Tyramine
* Others
* Cyclohexylamine
* Isoamylamine
* Trimethylamine

|

Exogenous|

* 2C-B
* 2C-B-Fly
* 2C-E
* 2C-H
* 2C-P
* 2C-T-7
* A-77636
* 2-Aminoindane
* Amphetamine
* AP163
* Apomorphine
* Asenapine
* Bromocriptine
* Cathinone
* Chlorpromazine
* Clonidine
* Cyproheptadine
* Dihydroergotamine
* Dimethyltryptamine
* DOB
* DOET
* DOI
* DOM
* N,N-Dimethylphenethylamine
* Ergometrine
* Fenoldopam
* Fenoterol
* 4-Fluoroamphetamine
* Guanabenz
* Guanfacine
* Halostachine
* Higenamine
* Hordenine
* 4-Hydroxyamphetamine (norpholedrine)
* Idazoxan
* 5-Iodo-2-aminoindane
* Isoprenaline
* Isopropyloctopamine
* Lisuride
* LK00764
* LSD
* MDA (tenamfetamine)
* MDAI
* MDMA (midomafetamine)
* Mescaline
* Metergoline
* N-Methyl-2-AI
* 2-Methylphenethylamine
* 3-Methylphenethylamine
* 4-Methylphenethylamine
* β-Methylphenethylamine
* Methamphetamine
* MMA
* MPTP
* Naphazoline
* Nomifensine
* Norfenfluramine
* Oxymetazoline
* Phentermine
* Phentolamine
* o-PIT
* Psilocin
* Ralmitaront (RG-7906, RO6889450)
* RG-7351
* RG-7410
* RO5073012
* RO5166017
* RO5203648
* RO5256390
* RO5263397
* S18616
* Selegiline (L-deprenyl)
* Solriamfetol
* Tolazoline
* Ulotaront (SEP-363856)

Antagonists|

* Compound 22
* EPPTB (RO-5212773)
* RTI-7470-44

Inverse agonists|

* EPPTB (RO-5212773)

TAAR5Tooltip Trace amine-associated receptor 5|

| Agonists|

* N,N-Dimethylethylamine
* Trimethylamine

|

Inverse agonists|

* 3-Iodothyronamine

Notes: (1) TAAR1 activity of ligands varies significantly between species. Some agents that are TAAR1 ligands in some species are not in other species. This navbox includes all TAAR1 ligands regardless of species. (2) See the individual pages for references, as well as the List of trace amines, TAAR, and TAAR1 pages.
See also: Receptor/signaling modulators

* v
* t
* e

Chemical classes of psychoactive drugs

Stimulants|

* Amphetamine-type/dopamine releasing agents: Alkylamines
* Cycloalkylaminopropanes
* Arylpiperazines
* Benzylpiperazines
* Phenylpiperazines
* Phenethylamines
* Aminorexes/phenyloxazolamines
* Amphetamines/α-methylphenethylamines
* Cathinones/β-ketoamphetamines
* β-Hydroxyamphetamines/cathinols
* Naphthylaminopropanes
* Phentermines
* Phenylisobutylamines/α-ethylphenethylamines
* α-Propylphenethylamines
* Phenylmorpholines/phenmetrazines
* Thiopropamines/thienylaminopropanes

* Cocaine-type/typical dopamine reuptake inhibitors: Phenethylamines
* Phenidates/benzylpiperidines
* Phenylethylpyrrolidines
* Pyrrolidinophenones
* Phenyltropanes/cocaine analogues

* Modafinil-type/atypical dopamine reuptake inhibitors: Modafinil analogues
* Phenylpiracetams

* Caffeine-type/adenosine receptor antagonists: Xanthines/methylxanthines

* Nicotine-type/nicotinic acetylcholine receptor agonists: Nicotine analogues

Depressants|

* GABAA receptor positive allosteric modulators: Alcohols/ethanol analogues
* Barbiturates
* Benzodiazepines
* Pyrrolobenzodiazepines
* Thienobenzodiazepines
* Thienodiazepines
* Thienotriazolodiazepines
* Triazolobenzodiazepines
* Carbamates
* Ethers
* Neuroactive steroids
* Nonbenzodiazepines
* β-Carbolines
* Cyclopyrrolones
* Imidazopyridines
* Pyrazolopyrimidines
* Phenols
* Piperidinediones
* Quinazolinones

* GABAA receptor agonists: Isoxazoles

* GHB receptor agonists: 1,4-Butanediols

* α2δ subunit-containing voltage-gated calcium channel blockers: Gabapentinoids

* Opioids/μ-opioid receptor agonists: Benzimidazoles
* Nitazenes
* Fentanyl analogues/phenylpiperidines
* Mitragyna alkaloids
* Morphinans/phenanthrenes
* Opiates/opium alkaloids
* Utopioids

* Antihistamines/H1 receptor antagonists: Benzimidazoles
* Diarylmethanes
* Ethylenediamines
* Tricyclics
* Dibenzocycloheptenes

Hallucinogens|

* Serotonergic psychedelics/serotonin 5-HT2A receptor agonists: Arylpiperazines
* Phenylpiperazines
* Quinolinylpiperazines
* Cyclized tryptamines
* Azepinoindoles
* Ibogalogs
* Iboga alkaloids
* β-Carbolines
* Harmala alkaloids
* Ergolines
* Lysergamides
* Simplified/partial lysergamides
* Phenethylamines (methoxyphenethylamines)
* 2Cs
* 25-NB/NBOMes
* 2C-Os
* 2C-Ts
* HOT-x
* TWEETIOs
* Amphetamines/α-methylphenethylamines
* 3Cs
* Dimethoxyamphetamines/DMAs
* DOx
* Alephs
* Methylenedioxyamphetamines/MDxx
* Trimethoxyamphetamines/TMAs
* BOx
* FLYs/benzofurans
* Phenylisobutylamines/α-ethylphenethylamines
* 4Cs
* Scalines
* Tryptamines
* α-Alkyltryptamines
* α-Alkyl-β-ketotryptamines
* 4-Hydroxytryptamines
* 5-Hydroxytryptamines
* 5-Methoxytryptamines
* Miscellaneous

* Dissociatives/NMDA receptor antagonists: Adamantanes
* Arylcyclohexylamines
* Diarylethylamines
* Morphinans

* κ-Opioid receptor agonists: Benzomorphans
* Salvinorins

* GABAA receptor agonists: Isoxazoles

* Deliriants/anticholinergics/muscarinic acetylcholine receptor antagonists: Diarylmethanes
* Tropanes

* Others: Cyclized tryptamines
* Azepinoindoles
* Iboga alkaloids
* (Phyto)cannabinoids

Entactogens|

* Serotonin releasing agents: Phenethylamines
* Aminoindanes
* Aminotetralins
* Amphetamines
* Benzofuranylaminopropanes
* Benzothiophenylaminopropanes
* Ethylenedioxyamphetamines
* Indanylaminopropanes
* Indolylaminopropanes
* Methylenedioxyamphetamine/MDxx
* Tetralinylaminopropanes
* Tryptamines
* α-Alkyltryptamines
* Miscellaneous

Psychiatric drugs|

* Anxiolytics: Azapirones
* Benzodiazepines
* Pyrrolobenzodiazepines
* Thienobenzodiazepines
* Thienodiazepines
* Thienotriazolodiazepines
* Triazolobenzodiazepines

* Antidepressants: Tricyclic antidepressants
* Dibenzazepines
* Dibenzocycloheptenes
* Dibenzothiepins
* Dibenzoxazepines
* Dibenzoxepins
* Tetracyclic antidepressants

* Antipsychotics/dopamine D2 receptor antagonists or partial agonists: Benzamides
* Benzimidazoles
* Benzisothiazoles
* Benzisoxazoles
* Butyrophenones
* Diphenylbutylpiperidines
* Phenylpiperazines
* Tricyclics
* Dibenzazepines
* Dibenzodiazepines
* Dibenzothiazepines
* Dibenzothiepins
* Dibenzoxazepines
* Phenothiazines
* Thienobenzodiazepines

* Mood stabilizers/anticonvulsants: Gabapentinoids
* Tricyclics
* Dibenzazepines
* Valproates

Others|

* Nootropics: Racetams
* Phenylpiracetams

* Miscellaneous: Adamantanes
* Catecholamines
* Tetrahydroisoquinolines
* Yohimbans

*[AU]: Australia
*[CA]: Canada
*[NZ]: New Zealand
*[UK]: United Kingdom
*[US]: United States
*[UN]: United Nations
*[CID]: Compound ID
*[EPA]: U.S. Environmental Protection Agency
*[EC50]: Half maximal effective concentration
*[NE]: Norepinephrine
*[DA]: Dopamine
*[5-HT]: Serotonin
*[ND]: No data
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[LD50]: median lethal dose
*[LDLo]: Lowest lethal dose
*[mRNA]: messenger RNA
*[DRAs]: Dopamine releasing agents
*[NRAs]: Norepinephrine releasing agents
*[SRAs]: Serotonin releasing agents
*[TAAR1]: Trace amine-associated receptor 1
*[TAAR5]: Trace amine-associated receptor 5