4-Methylamphetamine
{{short description|Stimulant and anorectic drug of the amphetamine class}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| verifiedrevid = 477222632
| IUPAC_name = 1-(4-methylphenyl)propan-2-amine
| image = 4-Methylamphetamine.svg
| image_class = skin-invert-image
| image2 = 4-Methylamphetamine molecule ball.png
| alt2 = Ball-and-stick model of the 4-methylamphetamine molecule
| tradename = Aptrol
| pregnancy_category =
| legal_CA = Schedule I
| legal_UK = Class A
| legal_DE = Anlage II
| legal_US = Schedule II (isomer of Methamphetamine)
| routes_of_administration = Oral, intranasal, injection,
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life = 6–12 hours
| excretion = Urine
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 64-11-9
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9E273KL7HS
| ATC_prefix = none
| PubChem = 199116
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 172349
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 166183
| synonyms = 4-MA; PAL-313; PAL313; p-TAP; Normephedrine
| C=10 | H=15 | N=1
| SMILES = NC(Cc1ccc(cc1)C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H15N/c1-8-3-5-10(6-4-8)7-9(2)11/h3-6,9H,7,11H2,1-2H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZDHZDWSHLNBTEB-UHFFFAOYSA-N
}}
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).
Pharmacology
In vitro, 4-methylamphetamine acts as a potent and well-balanced serotonin, norepinephrine, and dopamine releasing agent (SNDRA) with {{Abbrlink|EC50|half-maximal effective concentration}} values of 53.4{{nbsp}}nM, 22.2{{nbsp}}nM, and 44.1{{nbsp}}nM at the serotonin, norepinephrine, and dopamine transporters, respectively.{{cite journal | vauthors = Wee S, Anderson KG, Baumann MH, Rothman RB, Blough BE, Woolverton WL | title = Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 313 | issue = 2 | pages = 848–854 | date = May 2005 | pmid = 15677348 | doi = 10.1124/jpet.104.080101 | s2cid = 12135483 }} Receptor interaction data for 4-methylamphetamine have also been reported.{{cite journal | vauthors = Luethi D, Kolaczynska KE, Docci L, Krähenbühl S, Hoener MC, Liechti ME | title = Pharmacological profile of mephedrone analogs and related new psychoactive substances | journal = Neuropharmacology | volume = 134 | issue = Pt A | pages = 4–12 | date = May 2018 | pmid = 28755886 | doi = 10.1016/j.neuropharm.2017.07.026 | url = }}
However, more recent in vivo studies that involved performing microdialysis on rats showed a different trend. These studies showed that 4-methylamphetamine is much more potent at elevating serotonin (~18 x baseline) relative to dopamine (~5 x baseline). The authors speculated that this is because 5-HT release dampens DA release through some mechanism. For example, it was suggested that a possible cause for this could be activation of 5HT2C receptors since this is known to inhibit DA release. In addition there are alternative explanations such as 5-HT release then going on to encourage GABA release, which has an inhibitory effect on DA neurons.{{cite journal | vauthors = Di Giovanni G, Esposito E, Di Matteo V | title = Role of serotonin in central dopamine dysfunction | journal = CNS Neuroscience & Therapeutics | volume = 16 | issue = 3 | pages = 179–194 | date = June 2010 | pmid = 20557570 | pmc = 6493878 | doi = 10.1111/j.1755-5949.2010.00135.x }}
Research
4-MA was investigated as an appetite suppressant in 1952 and was even given a trade name, Aptrol, but development was apparently never completed.{{cite journal | vauthors = Gelvin EP, McGAVACK TH | title = 2-Amino-1-(p-methylphenyl)-propane (aptrol) as an anorexigenic agent in weight reduction | journal = New York State Journal of Medicine | volume = 52 | issue = 2 | pages = 223–226 | date = January 1952 | pmid = 14890975 }} More recently it has been reported as a novel designer drug.
In animal studies, 4-MA was shown to have the lowest rate of self-administration out of a range of similar drugs tested (the others being 3-methylamphetamine, 4-fluoroamphetamine, and 3-fluoroamphetamine), likely as a result of having the highest potency for releasing serotonin relative to dopamine.{{cite journal | vauthors = Baumann MH, Clark RD, Woolverton WL, Wee S, Blough BE, Rothman RB | title = In vivo effects of amphetamine analogs reveal evidence for serotonergic inhibition of mesolimbic dopamine transmission in the rat | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 337 | issue = 1 | pages = 218–225 | date = April 2011 | pmid = 21228061 | pmc = 3063744 | doi = 10.1124/jpet.110.176271 }}
Society and culture
More than a dozen deaths were reported throughout Europe in 2012-2013 after consumption of amphetamine ('speed') contaminated with 4-methylamphetamine.{{cite journal | vauthors = Blanckaert P, van Amsterdam J, Brunt T, van den Berg J, Van Durme F, Maudens K, van Bussel J | title = 4-Methyl-amphetamine: a health threat for recreational amphetamine users | journal = Journal of Psychopharmacology | volume = 27 | issue = 9 | pages = 817–822 | date = September 2013 | pmid = 23784740 | doi = 10.1177/0269881113487950 | s2cid = 35436194 }}{{Cite journal |title=4-Methyl-amphetamine: A health threat for recreational amphetamine users |url=https://www.researchgate.net/publication/240306373 |journal=ResearchGate}}{{cite journal | vauthors = Coppola M, Mondola R | title = 4-methylamphetamine (4-MA): chemistry, pharmacology and toxicology of a new potential recreational drug | journal = Mini Reviews in Medicinal Chemistry | volume = 13 | issue = 14 | pages = 2097–2101 | date = December 2013 | pmid = 24195663 | doi = 10.2174/13895575113136660106 }}
See also
References
{{Reflist}}
{{Stimulants}}
{{Anorectics}}
{{Monoamine releasing agents}}
{{Serotonin receptor modulators}}
{{Phenethylamines}}
{{DEFAULTSORT:Methylamphetamine, 4-}}