4-Methylamphetamine: Difference between revisions

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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 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 = 848–54 \| date = May 2005 \| pmid = 15677348 \| pmc = \| doi = 10.1124/jpet.104.080101 ~~\| url = https://semanticscholar.org/paper/52d9868fb317552827c712076eee1050347e7738~~ }}</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 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 = 179–94 \| date = June 2010 \| pmid = 20557570 \| pmc = 6493878\| doi = 10.1111/j.1755-5949.2010.00135.x \| url = https://iris.unipa.it/bitstream/10447/60783/1/Di%20Giovanni%20et%20al.%2c%202010%20%20CNS%20Neurosci%26Ther.pdf }}</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 \| s2cid = 12135483 \| 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 \| date = May 2005 \| pmid = 15677348 \| pmc = \| doi = 10.1124/jpet.104.080101 }}</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 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 = 179–94 \| date = June 2010 \| pmid = 20557570 \| pmc = 6493878\| doi = 10.1111/j.1755-5949.2010.00135.x \| url = https://iris.unipa.it/bitstream/10447/60783/1/Di%20Giovanni%20et%20al.%2c%202010%20%20CNS%20Neurosci%26Ther.pdf }}</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 = 223–6 \| date = January 1952 \| 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 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 = 223–6 \| 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>{{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 = 848–54 \| date = May 2005 \| pmid = 15677348 \| doi = 10.1124/jpet.104.080101 ~~\| url = https://semanticscholar.org/paper/52d9868fb317552827c712076eee1050347e7738~~ }}</ref><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 = 218–25 \| date = April 2011 \| pmid = 21228061 \| pmc = 3063744 \| doi = 10.1124/jpet.110.176271 }}</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 \| vauthors = Wee S, Anderson KG, Baumann MH, Rothman RB, Blough BE, Woolverton WL \| s2cid = 12135483 \| 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 \| date = May 2005 \| pmid = 15677348 \| doi = 10.1124/jpet.104.080101 }}</ref><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 = 218–25 \| date = April 2011 \| pmid = 21228061 \| pmc = 3063744 \| doi = 10.1124/jpet.110.176271 }}</ref>

	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 = 817–22 \| date = September 2013 \| pmid = 23784740 \| doi = 10.1177/0269881113487950 }}</ref>		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 = 817–22 \| date = September 2013 \| pmid = 23784740 \| doi = 10.1177/0269881113487950 }}</ref>

Revision as of 00:46, 3 June 2020

Pharmaceutical compound

4-Methylamphetamine
Clinical data


Routes of administration	Oral, intranasal, injection
ATC code	none
Legal status
Legal status	CA: Schedule I DE: Anlage II (Authorized trade only, not prescriptible) UK: Class A
Pharmacokinetic data
Elimination half-life	6-12 hours
Excretion	Urine
Identifiers
IUPAC name 1-(4-methylphenyl)propan-2-amine
CAS Number	22683-78-9
PubChem CID	199116
ChemSpider	172349
UNII	9E273KL7HS
ChEMBL	ChEMBL166183
CompTox Dashboard (EPA)	DTXSID50945351
Chemical and physical data
Formula	C₁₀H₁₅N
Molar mass	149.23 g/mol g·mol
3D model (JSmol)	Interactive image
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 K_i 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 5HT_2C 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 were reported throughout Europe in 2012-2013 after consumption of amphetamine ('speed') contaminated with 4-methylamphetamine.

References

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): 848–54. doi:10.1124/jpet.104.080101. PMID 15677348. S2CID 12135483.
Di Giovanni G, Esposito E, Di Matteo V (June 2010). "Role of serotonin in central dopamine dysfunction" (PDF). CNS Neuroscience & Therapeutics. 16 (3): 179–94. doi:10.1111/j.1755-5949.2010.00135.x. PMC 6493878. PMID 20557570.
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): 223–6. PMID 14890975.
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): 848–54. doi:10.1124/jpet.104.080101. PMID 15677348. S2CID 12135483.
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): 218–25. doi:10.1124/jpet.110.176271. PMC 3063744. PMID 21228061.
Blanckaert P, van Amsterdam J, Brunt T, van den Berg J, Van Durme F, Maudens K, van Bussel J (September 2013). "4-Methyl-amphetamine: a health threat for recreational amphetamine users". Journal of Psychopharmacology. 27 (9): 817–22. doi:10.1177/0269881113487950. PMID 23784740.

v t e Stimulants
Adamantanes	Adapromine Amantadine Bromantane Memantine Rimantadine
Adenosine antagonists	8-Chlorotheophylline 8-Cyclopentyltheophylline 8-Phenyltheophylline Aminophylline Caffeine CGS-15943 Dimethazan Istradefylline Paraxanthine SCH-58261 Theobromine Theophylline
Alkylamines	Cyclopentamine Cypenamine Cyprodenate Heptaminol Isometheptene Methylhexaneamine Octodrine Propylhexedrine Tuaminoheptane
Ampakines	CX-516 CX-546 CX-614 CX-691 CX-717 IDRA-21 LY-404,187 LY-503,430 Nooglutyl Org 26576 PEPA S-18986 Sunifiram Unifiram
Arylcyclohexylamines	Benocyclidine Dieticyclidine Esketamine Eticyclidine Gacyclidine Ketamine Phencyclamine Phencyclidine Rolicyclidine Tenocyclidine Tiletamine
Benzazepines	6-Br-APB SKF-77434 SKF-81297 SKF-82958
Cathinones	3-FMC 3-MMC 3,4-DMMC 4-BMC 4-CMC 4-Methylbuphedrone 4-Methylcathinone 4-MEAP 4-Methylpentedrone Amfepramone Benzedrone Buphedrone Bupropion Butylone Cathinone Dimethylcathinone Ethcathinone Ethylone Flephedrone Hexedrone Isoethcathinone Mephedrone Methcathinone Methedrone Methylenedioxycathinone Methylone Mexedrone N-Ethylbuphedrone N-Ethylhexedrone Pentedrone Pentylone Phthalimidopropiophenone
Cholinergics	A-84,543 A-366,833 ABT-202 ABT-418 AR-R17779 Altinicline Anabasine Arecoline Bradanicline Cotinine Cytisine Dianicline Epibatidine Epiboxidine GTS-21 Ispronicline Nicotine PHA-543,613 PNU-120,596 PNU-282,987 Pozanicline Rivanicline Sazetidine A SIB-1553A SSR-180,711 TC-1698 TC-1827 TC-2216 Tebanicline UB-165 Varenicline WAY-317,538
Convulsants	Anatoxin-a Bicuculline DMCM Flurothyl Gabazine Pentetrazol Picrotoxin Strychnine Thujone
Eugeroics	Adrafinil Armodafinil CRL-40,940 CRL-40,941 Fluorenol Modafinil
Oxazolines	4-Methylaminorex Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone
Phenethylamines	1-(4-Methylphenyl)-2-aminobutane 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane 2-Fluoroamphetamine 2-Fluoromethamphetamine 2-OH-PEA 2-Phenyl-3-aminobutane 2,3-MDA 3-Fluoroamphetamine 3-Fluoroethamphetamine 3-Methoxyamphetamine 3-Methylamphetamine 4-Fluoroamphetamine 4-Fluoromethamphetamine 4-MA 4-MMA 4-MTA 6-FNE AL-1095 Alfetamine a-Ethylphenethylamine Amfecloral Amfepentorex Amidephrine 2-Amino-1,2-dihydronaphthalene 2-Aminoindane 5-(2-Aminopropyl)indole 2-Aminotetralin Acridorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Arbutamine β-Methylphenethylamine β-Phenylmethamphetamine Benfluorex Benzphetamine BDB BOH 3-Benzhydrylmorpholine BPAP Camfetamine Cathine Chlorphentermine Cilobamine Cinnamedrine Clenbuterol Clobenzorex Cloforex Clortermine Cypenamine D-Deprenyl Denopamine Dimethoxyamphetamine Dimethylamphetamine Dobutamine DOPA (Dextrodopa, Levodopa) Dopamine Dopexamine Droxidopa EBDB Ephedrine Epinephrine Epinine Etafedrine Ethylnorepinephrine Etilamfetamine Etilefrine Famprofazone Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Feprosidnine Fludorex Formetorex Furfenorex Gepefrine Hexapradol HMMA Hordenine 4-Hydroxyamphetamine 5-Iodo-2-aminoindane Ibopamine Indanylamphetamine Iofetamine Isoetarine Isoprenaline L-Deprenyl (Selegiline) Lefetamine Lisdexamfetamine Lophophine MBDB MDA (tenamfetamine) MDBU MDEA MDMA (midomafetamine) MDMPEA MDOH MDPR MDPEA Mefenorex Mephentermine Metanephrine Metaraminol Mesocarb Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxamine Methoxyphenamine MMA Methoxyphenamine MMDA MMDMA MMMA Morforex N,alpha-Diethylphenylethylamine N,N-Dimethylphenethylamine Naphthylamphetamine Nisoxetine Norepinephrine Norfenefrine Norfenfluramine Normetanephrine L-Norpseudoephedrine Octopamine Orciprenaline Ortetamine Oxifentorex Oxilofrine PBA PCA PCMA PHA Pentorex Phenatine Phenpromethamine Phentermine Phenylalanine Phenylephrine Phenylpropanolamine Pholedrine PIA PMA PMEA PMMA PPAP Prenylamine Propylamphetamine Pseudoephedrine Ropinirole Salbutamol (Levosalbutamol) Sibutramine Solriamfetol Synephrine Theodrenaline Tiflorex Tranylcypromine Tyramine Tyrosine Xylopropamine Zylofuramine
Phenylmorpholines	3-Fluorophenmetrazine Fenbutrazate Fenmetramide G-130 Manifaxine Morazone Morforex Oxaflozane PD-128,907 Phendimetrazine Phenmetrazine 2-Phenyl-3,6-dimethylmorpholine Pseudophenmetrazine Radafaxine
Piperazines	2C-B-BZP 3C-PEP BZP CM156 DBL-583 GBR-12783 GBR-12935 GBR-13069 GBR-13098 GBR-13119 JJC8-088 MeOPP MBZP oMPP Vanoxerine
Piperidines	1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine 2-Benzylpiperidine 2-Methyl-3-phenylpiperidine 3,4-Dichloromethylphenidate 4-Benzylpiperidine 4-Fluoromethylphenidate 4-Methylmethylphenidate Desoxypipradrol Difemetorex Diphenylpyraline Ethylnaphthidate Ethylphenidate Methylnaphthidate Isopropylphenidate JZ-IV-10 Methylphenidate (Dexmethylphenidate) Nocaine Phacetoperane Pipradrol Propylphenidate Serdexmethylphenidate SCH-5472
Pyrrolidines	2-Diphenylmethylpyrrolidine 4-Cl-PVP 5-DBFPV α-PPP α-PBP α-PCYP α-PHiP α-PHP α-PHPP α-PVP α-PVT Diphenylprolinol DMPVP FPOP FPVP MDPPP MDPBP MPBP MPHP MPPP MOPVP MOPPP Indapyrophenidone MDPV Naphyrone PEP Picilorex Prolintane Pyrovalerone
Racetams	Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide
Tropanes	4-fluorotropacocaine 4'-Fluorococaine Altropane (IACFT) Brasofensine CFT (WIN 35,428) β-CIT (RTI-55) Cocaethylene Cocaine Dichloropane (RTI-111) Difluoropine FE-β-CPPIT FP-β-CPPIT Ioflupane (I) Norcocaine PIT PTT RTI-31 RTI-32 RTI-51 RTI-112 RTI-113 RTI-120 RTI-121 (IPCIT) RTI-126 RTI-150 RTI-177 RTI-229 RTI-336 RTI-354 RTI-371 RTI-386 Salicylmethylecgonine Tesofensine Troparil (β-CPT, WIN 35,065-2) Tropoxane WF-23 WF-33
Tryptamines	4-HO-αMT 4-Methyl-αET 4-Methyl-αMT 5-Chloro-αMT 5-Fluoro-αMT 5-MeO-αET 5-MeO-αMT 5-MeO-DIPT 6-Fluoro-αMT 7-Methyl-αET αET αMT
Others	2-MDP 3,3-Diphenylcyclobutanamine Amfonelic acid Amineptine Amiphenazole Atipamezole Atomoxetine Bemegride Benzydamine BTQ BTS 74,398 Centanafadine Ciclazindol Clofenciclan Cropropamide Crotetamide D-161 Desipramine Diclofensine Dimethocaine Efaroxan Etamivan Fenisorex Fenpentadiol Gamfexine Gilutensin GSK1360707F GYKI-52895 Hexacyclonate Idazoxan Indanorex Indatraline JNJ-7925476 Lazabemide Leptacline Lomevactone LR-5182 Mazindol Meclofenoxate Medifoxamine Mefexamide Methamnetamine Methastyridone Methiopropamine Naphthylaminopropane Nefopam Nikethamide Nomifensine O-2172 Oxaprotiline PNU-99,194 PRC200-SS Rasagiline Rauwolscine Rubidium chloride Setazindol Tametraline Tandamine Thiopropamine Thiothinone Trazium UH-232 Yohimbine
ATC code: N06B

Antiobesity agents/Anorectics (A08)

Stimulants

Amphetamines and phenethylamines	4-Methylamphetamine Amfecloral Amfepentorex Amfepramone Amphetamine Amphetaminil Benzphetamine Cathine Cathinone Chlorphentermine Clobenzorex Cloforex Clortermine Dextroamphetamine Dimethylcathinone Ephedrine Ephedra Etilamfetamine Etolorex Fenethylline Fenproporex Fludorex Furfenorex Khat Lisdexamfetamine Mefenorex Methamphetamine Norfenfluramine Pentorex Phentermine (+topiramate) Xylopropamine Zylofuramine
Adrenergic agonists	Albuterol Clenbuterol Ephedrine Ephedra Levopropylhexedrine Synephrine Terbutaline Yohimbine (Yohimbe)
Other	Aminorex Atomoxetine Benfluorex Bupropion (+naltrexone) Dexfenfluramine Dexmethylphenidate Difemetorex Fenbutrazate Fenfluramine (+phentermine) Manifaxine Mazindol Methylphenidate Phendimetrazine Phenethylamine Phenmetrazine Phenylpropanolamine Pipradrol Propylhexedrine Pyrovalerone Sibutramine Tesofensine

Cannabinoid
antagonists

GLP-1, GIP, and / or
glucagon agonists

DACRAs

Cagrilintide (+semaglutide)

5-HT2C
receptor agonists

Absorption inhibitors

Uncouplers

2,4-Dinitrophenol

Others

WHO-EM
Withdrawn from market
Clinical trials:
- Phase III
- Never to phase III

Monoamine releasing agents

DRAsTooltip Dopamine releasing agents

Morpholines: Fenbutrazate Fenmetramide Morazone Morforex Phendimetrazine Phenmetrazine Pseudophenmetrazine
Oxazolines: 4-MAR Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone
Phenethylamines: 2-OH-PEA 4-CAB 4-FA 4-FMA 4-MA 4-MMA Alfetamine Amfecloral Amfepentorex Amfepramone Amphetamine (Dextroamphetamine Levoamphetamine) Amphetaminil β-Me-PEA BDB BOH Benzphetamine Buphedrone Butylone Cathine Cathinone Clobenzorex Clortermine D-Deprenyl DMA DMMA Dimethylamphetamine Ephedrine Ethcathinone EBDB Ethylone Etilamfetamine Famprofazone Fenethylline Fenproporex Flephedrone Fludorex Furfenorex Hordenine 4-Hydroxyamphetamine Iofetamine (123I) Lisdexamfetamine Lophophine Mefenorex Mephedrone Metamfepramone Methamphetamine Dextromethamphetamine Levomethamphetamine Methcathinone Methedrone MMDA MMDMA MBDB MDA (tenamfetamine) MDEA MDMA (midomafetamine) MDMPEA MDOH MDPEA Methylone Morforex Ortetamine pBA pCA pIA Pholedrine Phenethylamine Pholedrine Phenpromethamine Prenylamine Propylamphetamine Pseudoephedrine Tiflorex Tyramine Xylopropamine Zylofuramine
Piperazines: 2C-B-BZP BZP MBZP MDBZP MeOPP oMPP
Others: 2-ADN 2-AI 2-AT 4-BP 5-APDI 5-IAI Amineptine Clofenciclan Cyclopentamine Cypenamine Cyprodenate Feprosidnine Gilutensin Heptaminol Hexacyclonate Indanorex Isometheptene Methylhexanamine Naphthylaminopropane Octodrine Phthalimidopropiophenone Phenylbiguanide Propylhexedrine

NRAsTooltip Norepinephrine releasing agents

Morpholines: Fenbutrazate Fenmetramide Morazone Morforex Phendimetrazine Phenmetrazine Pseudophenmetrazine
Oxazolines: 4-MAR Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone
Phenethylamines: 2-OH-PEA 4-CAB 4-FA 4-FMA 4-MA 4-MMA Alfetamine Amfecloral Amfepentorex Amfepramone Amphetamine Dextroamphetamine Levoamphetamine Amphetaminil β-Me-PEA BDB Benzphetamine BOH Buphedrone Butylone Cathine Cathinone Clobenzorex Clortermine Dimethylamphetamine DMA DMMA EBDB Ephedrine Ethcathinone Ethylone Etilamfetamine Famprofazone Fenethylline Fenproporex Flephedrone Fludorex Furfenorex Hordenine 4-Hydroxyamphetamine 5-APDI (IAP) Iofetamine (123I) Lisdexamfetamine Lophophine MBDB MDA (tenamfetamine) MDEA MDMA (midomafetamine) Metamfepramone MDMPEA MDOH MDPEA Mefenorex Mephedrone Mephentermine Methamphetamine Dextromethamphetamine Levomethamphetamine Methcathinone Methedrone Methylone Morforex Naphthylaminopropane Ortetamine pBA pCA Pentorex Phenethylamine Pholedrine Phenpromethamine Phentermine Phenylpropanolamine pIA Prenylamine Propylamphetamine Pseudoephedrine Selegiline (also D-Deprenyl) Tiflorex Tyramine Xylopropamine Zylofuramine
Piperazines: 2C-B-BZP BZP MBZP mCPP MDBZP MeOPP oMPP pFPP
Others: 2-ADN 2-AI 2-AT 2-BP 4-BP 5-IAI Clofenciclan Cyclopentamine Cypenamine Cyprodenate Feprosidnine Gilutensin Heptaminol Hexacyclonate Indanorex Isometheptene Methylhexanamine Octodrine Phthalimidopropiophenone Propylhexedrine Tuaminoheptane

SRAsTooltip Serotonin releasing agents

Aminoindanes: 5-IAI AMMI ETAI MDAI MDMAI MMAI TAI
Aminotetralins: 6-CAT 8-OH-DPAT MDAT MDMAT
Oxazolines: 4-Methylaminorex Aminorex Clominorex Fluminorex
Phenethylamines: 2-Methyl-MDA 4-CAB 4-FA 4-FMA 4-HA 4-MTA 5-APDB 5-Methyl-MDA 6-APDB 6-Methyl-MDA AEMMA Amiflamine BDB BOH Brephedrone Butylone Chlorphentermine Cloforex Amfepramone Metamfepramone DCA Dexfenfluramine DFMDA DMA DMMA EBDB EDMA Ethylone Etolorex Fenfluramine Flephedrone Flucetorex IAP Iofetamine Levofenfluramine Lophophine MBDB MDA (tenamfetamine) MDEA MDHMA MDMA (midomafetamine) MDMPEA MDOH MDPEA Mephedrone Methedrone Methylone MMA MMDA MMDMA MMMA NAP Norfenfluramine 4-TFMA pBA pCA pIA PMA PMEA PMMA TAP
Piperazines: 2C-B-BZP 3-MeOPP BZP DCPP MBZP mCPP MDBZP MeOPP Mepiprazole oMPP pCPP pFPP pTFMPP TFMPP
Tryptamines: 4-Methyl-αET 4-Methyl-αMT 5-CT 5-MeO-αET 5-MeO-αMT 5-MT αET αMT DMT Tryptamine
Others: Indeloxazine Viqualine

Others

DAT modulators: Agonist-like: SoRI-9804
SoRI-20040; Antagonist-like: SoRI-20041

Adrenergic release blockers: Bethanidine
Bretylium
Guanadrel
Guanazodine
Guanethidine
Guanoxan

See also: Receptor/signaling modulators • Monoamine reuptake inhibitors • Adrenergics • Dopaminergics • Serotonergics • Monoamine metabolism modulators • Monoamine neurotoxins

v t e Phenethylamines
Phenethylamines	Psychedelics: 25B-NBOMe 25C-NBOMe 25D-NBOMe 25I-NBOMe 25N-NBOMe 2C-B 2C-B-AN 2C-Bn 2C-Bu 2C-C 2C-CN 2C-CP 2C-D 2C-E 2C-EF 2C-F 2C-G 2C-G-1 2C-G-2 2C-G-3 2C-G-4 2C-G-5 2C-G-6 2C-G-N 2C-H 2C-I 2C-iP 2C-N 2C-NH2 2C-O 2C-O-4 2C-P 2C-Ph 2C-SE 2C-T 2C-T-2 2C-T-3 2C-T-4 2C-T-5 2C-T-6 2C-T-7 2C-T-8 2C-T-9 2C-T-10 2C-T-11 2C-T-12 2C-T-13 2C-T-14 2C-T-15 2C-T-16 2C-T-17 2C-T-18 2C-T-19 2C-T-20 2C-T-21 2C-T-22 2C-T-22.5 2C-T-23 2C-T-24 2C-T-25 2C-T-27 2C-T-28 2C-T-30 2C-T-31 2C-T-32 2C-T-33 2C-TFE 2C-TFM 2C-YN 2C-V Allylescaline DESOXY Escaline Isoproscaline Jimscaline Macromerine MEPEA Mescaline Metaescaline Methallylescaline Proscaline Psi-2C-T-4 TCB-2 Stimulants: Phenylethanolamine Hordenine Phenethylamine Phenpromethamine α-Methylphenethylamine (amphetamine) β-Methylphenethylamine m-Methylphenethylamine N-Methylphenethylamine o-Methylphenethylamine p-Methylphenethylamine Methylphenidate Entactogens: Lophophine MDPEA MDMPEA Others: BOH DMPEA
Amphetamines	Psychedelics: 3C-AL 3C-BZ 3C-E 3C-MAL 3C-P Aleph Beatrice Bromo-DragonFLY D-Deprenyl DMA DMCPA DMMDA DOB DOC DOEF DOET DOI DOM DON DOPR DOTFM Ganesha MMDA MMDA-2 Psi-DOM TMA TeMA ZDCM-04 Stimulants: 2-FA 2-FMA 3-FA 3-FMA Acridorex Alfetamine Amfecloral Amfepentorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Benfluorex Benzphetamine Cathine Clobenzorex Dimethylamphetamine Ephedrine Etilamfetamine Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Flucetorex Fludorex Formetorex Furfenorex Gepefrine 4-Hydroxyamphetamine Iofetamine Isopropylamphetamine Lefetamine Lisdexamfetamine Mefenorex Metaraminol Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxyphenamine MMA Morforex Norfenfluramine L-Norpseudoephedrine N,alpha-Diethylphenylethylamine Oxifentorex Oxilofrine Ortetamine PBA PCA PFA PFMA PIA PMA PMEA PMMA Phenylpropanolamine Pholedrine Prenylamine Propylamphetamine Pseudoephedrine Sibutramine Tiflorex Tranylcypromine Xylopropamine Zylofuramine Entactogens: 4-FA 4-FMA 4-MA 4-MMA 4-MTA 5-APB 5-APDB 5-EAPB 5-IT 5-MAPB 5-MAPDB 6-APB 6-APDB 6-Chloro-MDMA 6-EAPB 6-IT 6-MAPB 6-MAPDB EDA IAP 2,3-MDA 3,4-MDA (tenamfetamine) MDEA MDHMA MDMA (midomafetamine) MDOH Methamnetamine MMDMA Naphthylaminopropane TAP Others: 3,4-DCA Amiflamine DiFMDA Selegiline (also D-Deprenyl)
Phentermines	Stimulants: Chlorphentermine Cloforex Clortermine Etolorex Mephentermine Pentorex Phentermine Entactogens: MDPH MDMPH Others: Cericlamine
Cathinones	Stimulants: 3-FMC 4-MC 4-BMC 4-CMC 4-EMC 4-FMC 4-MEC 4-MeMABP 4-MPD Amfepramone Benzedrone Brephedrone Buphedrone Bupropion Cathinone Dimethylcathinone Ethcathinone Eutylone Hydroxybupropion Methcathinone Methedrone NEB N-Ethylhexedrone N-Ethylpentedrone Pentedrone Pentylone Radafaxine Entactogens: 3,4-DMMC 3-MMC Butylone Ethylone Methylone Methylenedioxycathinone Mephedrone
Phenylisobutylamines	Entactogens: 4-CAB 4-MAB Ariadne BDB Butylone EBDB Eutylone MBDB Stimulants: Phenylisobutylamine
Phenylalkylpyrrolidines	Stimulants: α-PBP α-PHP α-PPP α-PVP MDPBP MDPPP MDPV 4-MePBP 4-MePHP 4-MePPP MOPPP MOPVP MPBP MPHP MPPP Naphyrone PEP Prolintane Pyrovalerone
Catecholamines (and close relatives)	6-FNE 6-OHDA a-Me-DA a-Me-TRA Adrenochrome Ciladopa D-DOPA (Dextrodopa) Dimetofrine Dopamine Epinephrine Epinine Etilefrine Ethylnorepinephrine Fenclonine Ibopamine Isoprenaline Isoetarine L-DOPA (Levodopa) L-DOPS (Droxidopa) L-Phenylalanine L-Tyrosine m-Tyramine Metanephrine Metaraminol Metaterol Metirosine Methyldopa N,N-Dimethyldopamine Nordefrin (Levonordefrin) Norepinephrine Norfenefrine (m-Octopamine) Normetanephrine Orciprenaline p-Octopamine p-Tyramine Phenylephrine Synephrine
Miscellaneous	AL-LAD Amidephrine Arbutamine Cafedrine Denopamine Desvenlafaxine Diphenidine Dizocilpine Dobutamine Dopexamine Ephenidine Etafedrine ETH-LAD Famprofazone Fluorolintane Hexapradol IP-LAD Lysergic acid amide Lysergic acid 2-butyl amide Lysergic acid 2,4-dimethylazetidide Lysergic acid diethylamide Methoxamine Methoxphenidine MT-45 PARGY-LAD Phenibut PRO-LAD Pronethalol Salbutamol (Levosalbutamol) Solriamfetol Theodrenaline Thiamphenicol UWA-101 Venlafaxine

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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 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 = 848–54 \| date = May 2005 \| pmid = 15677348 \| pmc = \| doi = 10.1124/jpet.104.080101 ~~\| url = https://semanticscholar.org/paper/52d9868fb317552827c712076eee1050347e7738~~ }}</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 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 = 179–94 \| date = June 2010 \| pmid = 20557570 \| pmc = 6493878\| doi = 10.1111/j.1755-5949.2010.00135.x \| url = https://iris.unipa.it/bitstream/10447/60783/1/Di%20Giovanni%20et%20al.%2c%202010%20%20CNS%20Neurosci%26Ther.pdf }}</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 \| s2cid = 12135483 \| 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 \| date = May 2005 \| pmid = 15677348 \| pmc = \| doi = 10.1124/jpet.104.080101 }}</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 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 = 179–94 \| date = June 2010 \| pmid = 20557570 \| pmc = 6493878\| doi = 10.1111/j.1755-5949.2010.00135.x \| url = https://iris.unipa.it/bitstream/10447/60783/1/Di%20Giovanni%20et%20al.%2c%202010%20%20CNS%20Neurosci%26Ther.pdf }}</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 = 223–6 \| date = January 1952 \| 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 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 = 223–6 \| 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>{{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 = 848–54 \| date = May 2005 \| pmid = 15677348 \| doi = 10.1124/jpet.104.080101 ~~\| url = https://semanticscholar.org/paper/52d9868fb317552827c712076eee1050347e7738~~ }}</ref><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 = 218–25 \| date = April 2011 \| pmid = 21228061 \| pmc = 3063744 \| doi = 10.1124/jpet.110.176271 }}</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 \| vauthors = Wee S, Anderson KG, Baumann MH, Rothman RB, Blough BE, Woolverton WL \| s2cid = 12135483 \| 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 \| date = May 2005 \| pmid = 15677348 \| doi = 10.1124/jpet.104.080101 }}</ref><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 = 218–25 \| date = April 2011 \| pmid = 21228061 \| pmc = 3063744 \| doi = 10.1124/jpet.110.176271 }}</ref>

	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 = 817–22 \| date = September 2013 \| pmid = 23784740 \| doi = 10.1177/0269881113487950 }}</ref>		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 = 817–22 \| date = September 2013 \| pmid = 23784740 \| doi = 10.1177/0269881113487950 }}</ref>