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Revision as of 20:24, 2 July 2015 editNSH002 (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers, Rollbackers13,172 edits →References: fix, replaced: {{Serotonergics}} → {{Adrenergics}} using AWB← Previous edit Revision as of 02:18, 23 August 2015 edit undoPb0303 (talk | contribs)19 editsm literature updateTag: Visual editNext edit →
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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.


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 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>


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 ]. 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 ].
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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> 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>


More than a dozen deaths have been reported throughout Europe in 2012-2013 after consumption of amphetamine ('speed') contamined with 4-methylamphetamine.
== See also ==

Since 4-MA has little, if any, desirable psychoactive properties, researchers doubt the substance was added on purpose. A contaminated precursor, after synthesis yielding a mixture of amphetamine and 4-MA, seems the logical culprit<ref>{{Cite journal|title = 4-Methyl-amphetamine: a health threat for recreational amphetamine users|url = http://www.ncbi.nlm.nih.gov/pubmed/23784740|journal = Journal of Psychopharmacology (Oxford, England)|date = 2013-09-01|issn = 1461-7285|pmid = 23784740|pages = 817-822|volume = 27|issue = 9|doi = 10.1177/0269881113487950|first = P.|last = Blanckaert|first2 = Jgc|last2 = van Amsterdam|first3 = Tm|last3 = Brunt|first4 = Jdj|last4 = van den Berg|first5 = F.|last5 = Van Durme|first6 = K.|last6 = Maudens|first7 = Jch|last7 = van Bussel}}</ref>.
* ] * ]
* ] * ]

Revision as of 02:18, 23 August 2015

Pharmaceutical compound
4-Methylamphetamine
Ball-and-stick model of the 4-methylamphetamine molecule
Clinical data
ATC code
  • none
Identifiers
IUPAC name
  • 1-(4-methylphenyl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC10H15N
Molar mass149.23 g/mol 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.

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.

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.

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

Since 4-MA has little, if any, desirable psychoactive properties, researchers doubt the substance was added on purpose. A contaminated precursor, after synthesis yielding a mixture of amphetamine and 4-MA, seems the logical culprit.

References

  1. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 15677348, please use {{cite journal}} with |pmid=15677348 instead.
  2. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 20557570, please use {{cite journal}} with |pmid=20557570 instead.
  3. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 14890975 , please use {{cite journal}} with |pmid=14890975 instead.
  4. Wee, S; Anderson, KG; Baumann, MH; Rothman, RB; Blough, BE; Woolverton, WL (2005). "Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs". The Journal of Pharmacology and Experimental Therapeutics. 313 (2): 848–54. doi:10.1124/jpet.104.080101. PMID 15677348.
  5. Baumann, MH; Clark, RD; Woolverton, WL; Wee, S; Blough, BE; Rothman, RB. (Apr 2011). "In vivo effects of amphetamine analogs reveal evidence for serotonergic inhibition of mesolimbic dopamine transmission in the rat". Journal of Pharmacology and Experimental Therapeutics. 337 (1): 218–25. doi:10.1124/jpet.110.176271. PMC 3063744. PMID 21228061.
  6. Blanckaert, P.; van Amsterdam, Jgc; Brunt, Tm; van den Berg, Jdj; Van Durme, F.; Maudens, K.; van Bussel, Jch (2013-09-01). "4-Methyl-amphetamine: a health threat for recreational amphetamine users". Journal of Psychopharmacology (Oxford, England). 27 (9): 817–822. doi:10.1177/0269881113487950. ISSN 1461-7285. PMID 23784740.
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