"},"metabolites":{"wt":"[[Amphetamine]]"},"elimination_half-life":{"wt":""},"excretion":{"wt":"[[Urine]] (5–18% as [[amphetamine]])\n\n"},"CAS_number_Ref":{"wt":"{{cascite|correct|??}}"},"CAS_number":{"wt":"457-87-4"},"UNII_Ref":{"wt":"{{fdacite|correct|FDA}}"},"UNII":{"wt":"022YON1XMX"},"ATC_prefix":{"wt":"A08"},"ATC_suffix":{"wt":"AA06"},"PubChem":{"wt":"9982"},"ChemSpiderID_Ref":{"wt":"{{chemspidercite|correct|chemspider}}"},"ChemSpiderID":{"wt":"9588"},"KEGG_Ref":{"wt":"{{keggcite|correct|kegg}}"},"KEGG":{"wt":"D07114"},"ChEMBL_Ref":{"wt":"{{ebicite|correct|EBI}}"},"ChEMBL":{"wt":"276443"},"synonyms":{"wt":"Etilamfetamine; Ethylamphetamine; ''N''-Ethylamphetamine; PAL-99; PAL99\n\n"},"C":{"wt":"11"},"H":{"wt":"17"},"N":{"wt":"1"},"SMILES":{"wt":"N(C(Cc1ccccc1)C)CC"},"StdInChI_Ref":{"wt":"{{stdinchicite|correct|chemspider}}"},"StdInChI":{"wt":"1S/C11H17N/c1-3-12-10(2)9-11-7-5-4-6-8-11/h4-8,10,12H,3,9H2,1-2H3"},"StdInChIKey_Ref":{"wt":"{{stdinchicite|correct|chemspider}}"},"StdInChIKey":{"wt":"YAGBSNMZQKEFCO-UHFFFAOYSA-N"}},"i":0}}]}" id="mwBA">Pharmaceutical compound
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Clinical data | |
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Trade names | Apetinil; Adiparthrol |
Other names | Etilamfetamine; Ethylamphetamine; N-Ethylamphetamine; PAL-99; PAL99 |
Routes of administration | Oral, sublingual, insufflated, inhaled (vaporized), intravenous, rectal |
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Pharmacokinetic data | |
Metabolism | Hepatic (N-dealkylation, others) [2] |
Metabolites | Amphetamine [2] |
Excretion | Urine (5–18% as amphetamine) [2] |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.230.711 |
Chemical and physical data | |
Formula | C11H17N |
Molar mass | 163.264 g·mol−1 |
3D model (JSmol) | |
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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 is a potent dopamine releasing agent (DRA) in vitro , with an EC50 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]
Compound | NE | DA | 5-HT | Ref | ||
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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] |
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 Ki was 2,500 nM and its EC50 (Emax ) was 880 nM (62%) at the rat TAAR1 (i.e., it was a partial agonist), whereas its Ki 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]
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]
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.
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 ]
Cathine, also known as D-norpseudoephedrine or as (+)-norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine groups which acts as a stimulant. Along with cathinone, it is found naturally in Catha edulis (khat), and contributes to the overall effects of the plant. Cathine has approximately 7 to 10% of the potency of amphetamine.
Phentermine, sold under the brand name Adipex-P among others, is a medication used together with diet and exercise to treat obesity. It is available by itself or as the combination phentermine/topiramate. Phentermine is taken by mouth.
Phenmetrazine, sold under the brand name Preludin among others, is a stimulant drug first synthesized in 1952 and originally used as an appetite suppressant, but withdrawn from the market in the 1980s due to widespread misuse. It was initially replaced by its analogue phendimetrazine which functions as a prodrug to phenmetrazine, but now it is rarely prescribed, due to concerns of misuse and addiction. Chemically, phenmetrazine is a substituted amphetamine containing a morpholine ring or a substituted phenylmorpholine.
Aminorex, sold under the brand names Menocil and Apiquel among others, is a weight loss (anorectic) stimulant drug. It was withdrawn from the market after it was found to cause pulmonary hypertension (PPH). In the United States, aminorex is a Schedule I controlled substance.
Chlorphentermine, sold under the brand names Apsedon, Desopimon, and Lucofen, is a serotonergic appetite suppressant of the amphetamine family. Developed in 1962, it is the para-chloro derivative of the better-known appetite suppressant phentermine, which is still in current use.
Propylamphetamine is a psychostimulant of the amphetamine family which was never marketed. It was first developed in the 1970s, mainly for research into the metabolism of, and as a comparison tool to, other amphetamines.
Naphthylaminopropane, also known as naphthylisopropylamine (NIPA), is an experimental drug that was under investigation for the treatment of alcohol and stimulant addiction.
Norfenfluramine, or 3-trifluoromethylamphetamine, is a never-marketed drug of the amphetamine family and a major active metabolite of the appetite suppressants fenfluramine and benfluorex. The compound is a racemic mixture of two enantiomers with differing activities, dexnorfenfluramine and levonorfenfluramine.
A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitters and hence enhanced signaling by those neurotransmitters. The monoamine neurotransmitters include serotonin, norepinephrine, and dopamine; MRAs can induce the release of one or more of these neurotransmitters.
A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain.
4-Methylamphetamine (4-MA), also known by the former proposed brand name Aptrol, is a stimulant and anorectic drug of the amphetamine family. It is structurally related to mephedrone (4-methylmethcathinone).
4-Methylmethamphetamine (4-MMA), also known as mephedrine, is a putative stimulant and entactogen drug of the amphetamine family. It acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA). The drug is the β-deketo analogue of mephedrone and the N-methyl analogue of 4-methylamphetamine (4-MA).
Pseudophenmetrazine is a psychostimulant of the phenylmorpholine group. It is the N-demethylated and cis-configured analogue of phendimetrazine as well as the cis-configured stereoisomer of phenmetrazine. In addition, along with phenmetrazine, it is believed to be one of the active metabolites of phendimetrazine, which itself is inactive and behaves merely as a prodrug.
4,4'-Dimethylaminorex, sometimes referred to by the street name "Serotoni", is a psychostimulant and entactogen designer drug related to aminorex, 4-methylaminorex, and pemoline. It was first detected in the Netherlands in December 2012, and has been sold as a designer drug around Europe since mid-2013.
Methamnetamine is a triple monoamine releasing agent and N-methyl analog of the non-neurotoxic experimental drug naphthylaminopropane and the naphthalene analog of methamphetamine. It has been sold online as a designer drug.
3',4'-Methylenedioxy-4-methylaminorex (MDMAR) is a recreational designer drug from the substituted aminorex family, with monoamine-releasing effects. It is a potent serotonin–norepinephrine–dopamine releasing agent (SNDRA).
BMAPN, also known as βk-methamnetamine or as 2-naphthylmethcathinone, is a substituted cathinone derivative with stimulant effects. It inhibits dopamine reuptake and has rewarding and reinforcing properties in animal studies. It is banned under drug analogue legislation in a number of jurisdictions. The drug was at one point marketed under the name NRG-3, although only a minority of samples of substances sold under this name have been found to actually contain BMAPN, with most such samples containing mixtures of other cathinone derivatives.
Butylamphetamine is a psychostimulant of the substituted amphetamine family which was never marketed.
Ethylnaphthylaminopropane is a monoamine releasing agent (MRA) of the amphetamine family that is related to naphthylaminopropane and methamnetamine. It acts specifically as a serotonin–norepinephrine–dopamine releasing agent (SNDRA). However, ENAP is unusual in being a partial releaser of serotonin and dopamine and a full releaser of norepinephrine.
Naphthylmetrazine, also known as 3-methyl-2-(2′-naphthyl)morpholine, is a monoamine releasing agent (MRA) and monoamine reuptake inhibitor (MRI) of the phenylmorpholine family related to phenmetrazine. It is the analogue of phenmetrazine in which the phenyl ring has been replaced with a naphthalene ring.
FIGURE 2-6: Release: Effects of the specified test drug on monoamine release by DAT (red circles), NET (blue squares), and SERT (black traingles) in rat brain tissue. [...] EC50 values determined for the drug indicated within the panel. [...]
RESULTS. Methamphetamine and amphetamine potently released NE (IC50s = 14.3 and 7.0 nM) and DA (IC50s = 40.4 nM and 24.8 nM), and were much less potent releasers of 5-HT (IC50s = 740 nM and 1765 nM). [...]