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{{short description|Stimulant and anorectic drug of the amphetamine class}}
{{Drugbox
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = changed | Verifiedfields = changed
| verifiedrevid = 477222632 | verifiedrevid = 477222632
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<!--Clinical data--> <!--Clinical data-->
| tradename = | tradename =
| pregnancy_category = | pregnancy_category =
| legal_status = | legal_CA = Schedule I
| legal_UK = Class A
⚫ | routes_of_administration =
| legal_DE = Anlage II
| legal_US = ]
⚫ | routes_of_administration = Oral, intranasal, injection,


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = | bioavailability =
| metabolism = | metabolism =
| elimination_half-life = | elimination_half-life = 6-12 hours
| excretion = | excretion = Urine


<!--Identifiers--> <!--Identifiers-->
| CAS_number_Ref = {{cascite|changed|??}} | CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 22683-78-9 | CAS_number = 64-11-9
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9E273KL7HS
| ATC_prefix = none | ATC_prefix = none
| PubChem = 199116 | PubChem = 199116
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<!--Chemical data--> <!--Chemical data-->
| C=10 | H=15 | N=1 | C=10 | H=15 | N=1
| molecular_weight = 149.23 g/mol
| smiles = NC(Cc1ccc(cc1)C)C | smiles = NC(Cc1ccc(cc1)C)C
| InChI = 1/C10H15N/c1-8-3-5-10(6-4-8)7-9(2)11/h3-6,9H,7,11H2,1-2H3
| InChIKey = ZDHZDWSHLNBTEB-UHFFFAOYAG
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | 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 | StdInChI = 1S/C10H15N/c1-8-3-5-10(6-4-8)7-9(2)11/h3-6,9H,7,11H2,1-2H3
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}} }}


'''4-Methylamphetamine''' ('''4-MA'''; '''PAL-313'''; '''Aptrol'''; '''p-TAP''') is a ] and ] ] of the ] and ] ]es. '''4-Methylamphetamine''' ('''4-MA'''; '''PAL-313'''; '''Aptrol'''; '''p-TAP''') is a ] and ] ] of the ] and ] ]es.


== Pharmacology ==
⚫ In vitro, it acts as a ] and ] ], ], and ] ] with ] ] values of 53.4nM, 22.2nM, and 44.1nM at the ], ], and ]s, respectively.<ref name="pmid15677348">{{Cite pmid|15677348}}</ref> 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 5HT<sub>2C</sub> 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.<ref>{{Cite pmid|20557570}}</ref>


⚫ In vitro, it acts as a ] and ] ], ], and ] ] with ] ] values of 53.4nM, 22.2nM, and 44.1nM at the ], ], and ]s, respectively.<ref name="pmid15677348">{{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 }}</ref> 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 ] (~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 5HT<sub>2C</sub> 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.<ref>{{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 }}</ref>
⚫ 4-MA was investigated as an ] in 1952 and was even given a trade name, '''Aptrol''', but development was apparently never completed.<ref name="pmid14890975">{{Cite pmid|14890975 }}</ref> More recently it has been reported as a novel ].


== Research ==
⚫ 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 ], ], and ]), likely as a result of having the highest potency for releasing serotonin relative to dopamine.<ref>{{cite journal | last1 = Wee | first1 = S | last2 = Anderson | first2 = KG | last3 = Baumann | first3 = MH | last4 = Rothman | first4 = RB | last5 = Blough | first5 = BE | last6 = Woolverton | first6 = 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 = 848–54 | year = 2005 | pmid = 15677348 | doi = 10.1124/jpet.104.080101 }}</ref><ref>{{cite journal | last1 = Baumann | first1 = MH | last2 = Clark | first2 = RD | last3 = Woolverton | first3 = WL | last4 = Wee | first4 = S | last5 = Blough | first5 = BE | last6 = Rothman | first6 = RB. |date=Apr 2011 | title = In vivo effects of amphetamine analogs reveal evidence for serotonergic inhibition of mesolimbic dopamine transmission in the rat | url = | journal = Journal of Pharmacology and Experimental Therapeutics | volume = 337 | issue = 1| pages = 218–25 | doi = 10.1124/jpet.110.176271 | pmid = 21228061 | pmc=3063744}}</ref>

⚫ 4-MA was investigated as an ] in 1952 and was even given a trade name, '''Aptrol''', but development was apparently never completed.<ref name="pmid14890975">{{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 }}</ref> More recently it has been reported as a novel ].

⚫ 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 ], ], and ]), likely as a result of having the highest potency for releasing serotonin relative to dopamine.<ref name="pmid15677348"/><ref>{{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 }}</ref>

== Society and culture ==

More than a dozen deaths were reported throughout Europe in 2012-2013 after consumption of amphetamine ('speed') contaminated with 4-methylamphetamine.<ref>{{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 }}</ref><ref>{{Cite journal |title=4-Methyl-amphetamine: A health threat for recreational amphetamine users |url=https://www.researchgate.net/publication/240306373 |journal=ResearchGate}}</ref><ref>{{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 }}</ref>


== See also == == See also ==
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* ] * ]
* ] * ]
* ]
* ] * ]
* ] * ]
* ]


== References == == References ==
{{Reflist}} {{Reflist}}



{{Stimulants}} {{Stimulants}}
{{Anorectics}} {{Anorectics}}
{{Monoamine releasing agents}}
{{Monoaminergics}}
{{Phenethylamines}} {{Phenethylamines}}


{{DEFAULTSORT:Methylamphetamine, 4-}} {{DEFAULTSORT:Methylamphetamine, 4-}}

] ]
] ]

Latest revision as of 12:43, 27 July 2024

Stimulant and anorectic drug of the amphetamine class

Pharmaceutical compound
4-Methylamphetamine
Ball-and-stick model of the 4-methylamphetamine molecule
Clinical data
Routes of
administration		Oral, intranasal, injection,
ATC code
  • none
Legal status
Legal status
Pharmacokinetic data
Elimination half-life6-12 hours
ExcretionUrine
Identifiers
IUPAC name
  • 1-(4-methylphenyl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC10H15N
Molar mass149.237 g·mol
3D model (JSmol)
SMILES
  • NC(Cc1ccc(cc1)C)C
InChI
  • InChI=1S/C10H15N/c1-8-3-5-10(6-4-8)7-9(2)11/h3-6,9H,7,11H2,1-2H3
  • Key:ZDHZDWSHLNBTEB-UHFFFAOYSA-N
  (what is this?)  (verify)

4-Methylamphetamine (4-MA; PAL-313; Aptrol; p-TAP) is a stimulant and anorectic drug of the phenethylamine and amphetamine chemical classes.

Pharmacology

In vitro, it acts as a potent and balanced serotonin, norepinephrine, and dopamine releasing agent with Ki affinity values of 53.4nM, 22.2nM, and 44.1nM at the serotonin, norepinephrine, and dopamine transporters, respectively. 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.

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. 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.

Society and culture

More than a dozen deaths were reported throughout Europe in 2012-2013 after consumption of amphetamine ('speed') contaminated with 4-methylamphetamine.

See also

References

  1. ^ Wee S, Anderson KG, Baumann MH, Rothman RB, Blough BE, Woolverton WL (May 2005). "Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs". The Journal of Pharmacology and Experimental Therapeutics. 313 (2): 848–854. doi:10.1124/jpet.104.080101. PMID 15677348. S2CID 12135483.
  2. Di Giovanni G, Esposito E, Di Matteo V (June 2010). "Role of serotonin in central dopamine dysfunction". CNS Neuroscience & Therapeutics. 16 (3): 179–194. doi:10.1111/j.1755-5949.2010.00135.x. PMC 6493878. PMID 20557570.
  3. Gelvin EP, McGAVACK TH (January 1952). "2-Amino-1-(p-methylphenyl)-propane (aptrol) as an anorexigenic agent in weight reduction". New York State Journal of Medicine. 52 (2): 223–226. PMID 14890975.
  4. Baumann MH, Clark RD, Woolverton WL, Wee S, Blough BE, Rothman RB (April 2011). "In vivo effects of amphetamine analogs reveal evidence for serotonergic inhibition of mesolimbic dopamine transmission in the rat". The Journal of Pharmacology and Experimental Therapeutics. 337 (1): 218–225. doi:10.1124/jpet.110.176271. PMC 3063744. PMID 21228061.
  5. Blanckaert P, van Amsterdam J, Brunt T, van den Berg J, Van Durme F, Maudens K, et al. (September 2013). "4-Methyl-amphetamine: a health threat for recreational amphetamine users". Journal of Psychopharmacology. 27 (9): 817–822. doi:10.1177/0269881113487950. PMID 23784740. S2CID 35436194.
  6. "4-Methyl-amphetamine: A health threat for recreational amphetamine users". ResearchGate.
  7. Coppola M, Mondola R (December 2013). "4-methylamphetamine (4-MA): chemistry, pharmacology and toxicology of a new potential recreational drug". Mini Reviews in Medicinal Chemistry. 13 (14): 2097–2101. doi:10.2174/13895575113136660106. PMID 24195663.
Stimulants
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