Etilamfetamine

Etilamfetamine, also known as N-ethylamphetamine and formerly sold under the brand names Apetinil and Adiparthrol, is a stimulant drug of the amphetamine family. It was invented in the early 20th century and was subsequently used as an anorectic or appetite suppressant in the 1950s,^[3] but was not as commonly used as other amphetamines such as amphetamine, methamphetamine, and benzphetamine, and was largely discontinued once newer drugs such as phenmetrazine were introduced.

Ethylamphetamine
INN: Etilamfetamine

Clinical data
Trade names	Apetinil; Adiparthrol
Other names	Etilamfetamine; Ethylamphetamine; N-Ethylamphetamine; PAL-99; PAL99
Routes of administration	Oral, sublingual, insufflated, inhaled (vaporized), intravenous, rectal
ATC code	A08AA06 (WHO)
Legal status
Legal status	BR: Class B1 (Psychoactive drugs)[1] CA: Schedule I DE: Anlage II (Authorized trade only, not prescriptible) UK: Class C US: Schedule I
Pharmacokinetic data
Metabolism	Hepatic (N-dealkylation, others)[2]
Metabolites	Amphetamine[2]
Excretion	Urine (5–18% as amphetamine)[2]
Identifiers
IUPAC name N-Ethyl-1-phenyl-propan-2-amine
CAS Number	457-87-4 Y
PubChem CID	9982
ChemSpider	9588 Y
UNII	022YON1XMX
KEGG	D07114 Y
ChEMBL	ChEMBL276443 Y
CompTox Dashboard (EPA)	DTXSID10860359
ECHA InfoCard	100.230.711
Chemical and physical data
Formula	C11H17N
Molar mass	163.264 g·mol−1
3D model (JSmol)	Interactive image
SMILES N(C(Cc1ccccc1)C)CC
InChI InChI=1S/C11H17N/c1-3-12-10(2)9-11-7-5-4-6-8-11/h4-8,10,12H,3,9H2,1-2H3 Y Key:YAGBSNMZQKEFCO-UHFFFAOYSA-N Y
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Pharmacology

Pharmacodynamics

Monoamine releasing agent

Ethylamphetamine is a potent dopamine releasing agent (DRA) in vitro, with an EC₅₀Tooltip half-maximal effective concentration of 88.5 nM.^[4] This is about 10-fold lower than the EC₅₀ of dextroamphetamine.^[4] The EC₅₀ values of ethylamphetamine for induction of norepinephrine and serotonin release were not reported.^[4] However, the EC₅₀ values of its dextrorotatory enantiomer dextroethylamphetamine have been reported and were 44.1 nM, 28.8 nM, and 333 nM for norepinephrine, dopamine, and serotonin, respectively.^[5][6] Hence, dextroethylamphetamine acts as a norepinephrine–dopamine releasing agent (NDRA) with weak effects on serotonin.^[5][6]

In terms of structure–activity relationships, the potency of amphetamines as dopamine releasing agents and reuptake inhibitors decreases with increasing N-alkyl chain length.^[4] That is, the order of potency of N-alkylated amphetamines is as follows: amphetamine > methamphetamine > ethylamphetamine > propylamphetamine > butylamphetamine.^[4] Propylamphetamine is a weak dopamine reuptake inhibitor rather than releaser, whereas butylamphetamine is completely inactive as a dopamine releaser or reuptake inhibitor.^[4] The same relationship, for monoamine release and reuptake inhibition generally, has been shown with 4-methylamphetamine and its N-alkylated derivatives like 4-methylmethamphetamine and so forth.^[7][8]

Monoamine release of ethylamphetamine 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	[4][9][10]
d-Amphetamine	6.6–10.2	5.8–24.8	698–1,765	[11][12][10][13]
d-Methamphetamine	12.3–14.3	8.5–40.4	736–1,292	[11][14][10][13]
Ethylamphetamine	ND	88.5	ND	[4]
d-Ethylamphetamine	28.8	44.1	333.0	[5][6]
Propylamphetamine	ND	RI (1,013)	ND	[4]
Butylamphetamine	ND	IA (>10,000)	ND	[4]
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: [15][16]

Other actions

Ethylamphetamine is inactive as an agonist of the mouse and human trace amine-associated receptor 1 (TAAR1), whereas findings in the case of the rat TAAR1 are conflicting.^[17][18] In one study, its K_i was 2,500 nM and its EC₅₀Tooltip half-maximal effective concentration (E_maxTooltip maximal efficacy) was 880 nM (62%) at the rat TAAR1 (i.e., it was a partial agonist), whereas its K_i and/or EC₅₀ values at the mouse and human TAAR1 were >10,000 nM.^[17] In another study however, ethylamphetamine showed very little capacity to activate the rat TAAR1.^[17]

Pharmacokinetics

Ethylamphetamine can be N-dealkylated into amphetamine (5–18% excreted in urine after 24 hours).^[2] As such, amphetamine may contribute to its effects in vivo.^[2]

Chemistry

The molecular structure of ethylamphetamine is analogous to methamphetamine, with an ethyl group in place of the methyl group.^{[Note 1]} It can also be considered a substituted amphetamine, with an ethyl group on the amphetamine backbone.^{[Note 2][Note 3]}

Analogues of ethylamphetamine include amphetamine, methamphetamine, propylamphetamine, isopropylamphetamine, butylamphetamine, fenfluramine (3-trifluoromethyl-N-ethylamphetamine), dimethylamphetamine, and 3-fluoroethamphetamine (3-fluoro-N-ethylamphetamine), among others.

Society and culture

Recreational use

Ethylamphetamine can be used as a recreational drug and, while its prevalence is less than amphetamine's, it is still encountered as a substance taken for recreational purposes. Ethylamphetamine produces effects similar to amphetamine and methamphetamine, though it is of lower potency.^{[citation needed]}

Notes

1. Amphetamine is a substituted phenethylamine with a methyl group at R^A position.
2. The ethyl group of ethylamphetamine is at R^N position, hence the name N-ethylamphetamine.
3. Ethylamphetamine is structurally similar to N-methylamphetamine (methamphetamine), the ethyl group being replaced in methamphetamine with a methyl group.