Β-Methylphenethylamine: Difference between revisions

{{Short description|Chemical compound}}

{{Use dmy dates|date=April 2015}}

| verifiedrevid = 449584722

| IUPAC_name = 2-Phenylpropan-1-amine

| image2 = Beta-Methylphenethylamine molecule ball.png

| drug_name = β-Methylphenethylamine

| legal_status =

| legal_US = Unapproved "New Drug" (as defined by 21 U.S. Code § 321(p)(1)). Use in [[dietary supplement]]s, [[food]], or [[medicine]] is unlawful; otherwise uncontrolled.<ref>{{Cite web |date=February 22, 2023 |title=BMPEA in Dietary Supplements |url=https://www.fda.gov/food/dietary-supplement-ingredient-directory/bmpea-dietary-supplements |access-date=June 9, 2023 |website=[[FDA]]}}</ref>

| routes_of_administration =

| excretion =

| CAS_number_Ref = {{cascite|correct|PubChem}}

| CAS_number = 582-22-9

| ATC_prefix = none

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 6XL7O3V13L

| ChEMBL = 158578

| ChEBI = 229522

| C=9 | H=13 | N=1

| density = 0.93

| boiling_point = 80

| boiling_notes = (at 10 mm Hg)

'''β-Methylphenethylamine''' ('''β-Me-PEA''', '''BMPEA''', or '''1-amino-2-phenylpropane''') is an [[organic compound]] of the [[phenethylamine]] class, and a [[positional isomer]] of the drug [[amphetamine]], with which it shares some properties. In particular, both amphetamine and β-methylphenethylamine are human [[TAAR1]] agonists.<ref name="pmid17038507">{{cite journal | vauthors = Wainscott DB, Little SP, Yin T, Tu Y, Rocco VP, He JX, Nelson DL | title = Pharmacologic characterization of the cloned human trace amine-associated receptor1 (TAAR1) and evidence for species differences with the rat TAAR1 | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 320 | issue = 1 | pages = 475–485 | date = January 2007 | pmid = 17038507 | doi = 10.1124/jpet.106.112532 | quote = The effect of β-carbon substitution on the phenylethylamine side chain was also investigated (Table 3). A β-methyl substituent was well tolerated compared with β-PEA. In fact, S-(–)-β-methyl-β-PEA was as potent as β-PEA at human TAAR1. | s2cid = 10829497 }}</ref> In appearance, it is a colorless or yellowish liquid.

Relatively little information has been published about this substance. Hartung and Munch reported that it had good [[antihypotensive agent|antihypotensive]] (pressor) activity in experimental animals, and that it was orally active. The MLD (minimum lethal dose) for the HCl salt was given as 500&nbsp;mg/kg (rat, s.c.) and 50&nbsp;mg/kg (rabbit, i.v.).<ref name = Hartung>{{ cite journal | vauthors = Hartung WH, Munch JC | title = Amino alcohols. VI. The preparation and pharmacodynamic activity of four isomeric phenylpropylamines | journal = J. Am. Chem. Soc. | year = 1931 | volume = 53 | issue = 5 | pages = 1875–9 | doi = 10.1021/ja01356a036 }}</ref>

A study by Graham and co-workers at the Upjohn Co., comparing many β-methylphenethylamines substituted on the benzene ring showed that β-methylphenethylamine itself had 1/700 x the pressor activity of [[epinephrine]], corresponding to ~ 1/3 the potency of amphetamine. The β-methyl compound also had ~ 2 x the broncho-dilating power of amphetamine (as measured using the isolated rabbit lung), and an LD₅₀ of 50&nbsp;mg/kg (rat, i.v.).<ref>{{ cite journal | vauthors = Graham BE, Cartland GF, Woodruff EH | title = Phenyl propyl and phenyl isopropyl amines. Changes in pharmacological action on substitution of phenyl nucleus and amino nitrogen | journal = Ind. Eng. Chem. | year = 1945 | volume = 37 | issue = 2 | pages = 149–51 | doi = 10.1021/ie50422a010 }}</ref>

==Synthesis==

β-Methylphenethylamine can be made by the [[catalytic]] [[hydrogenation]] of 2-phenylpropionitrile with [[Pd/C]] in pure anhydrous ethanol containing three equivalents of HCl; the finished product is extracted as the HCl salt, m.p.&nbsp;123-124°.<ref name = Hartung/>

== Presence ==

In 2015, 52% of supplements labeled as containing ''[[Acacia rigidula]]'' were found to contain BMPEA.<ref name=cohen2015>{{cite journal | vauthors = Cohen PA, Bloszies C, Yee C, Gerona R | title = An amphetamine isomer whose efficacy and safety in humans has never been studied, β-methylphenylethylamine (BMPEA), is found in multiple dietary supplements | journal = Drug Testing and Analysis | volume = 8 | issue = 3–4 | pages = 328–333 | year = 2016 | pmid = 25847603 | doi = 10.1002/dta.1793 | doi-access = free }}</ref><ref>{{cite news | vauthors = ((The Editorial Board)) |title=Conflicts of Interest at the F.D.A. |url=https://www.nytimes.com/2015/04/13/opinion/conflicts-of-interest-at-the-fda.html |quote= they identified BMPEA in 11 of 21 brands of supplements with acacia rigidula listed as an ingredient.|newspaper=[[The New York Times]] |date=April 13, 2015 |access-date=2015-04-13 }}</ref> Consumers following recommended maximum daily servings would consume a maximum of 94&nbsp;mg of BMPEA per day.<ref name=cohen2015/> In 2012, however, the FDA determined that BMPEA was not naturally present in ''Acacia rigidula'' leaves.<ref>{{cite web|url=http://www.webmd.com/vitamins-and-supplements/news/20150407/bmpea-acacia-rigidula-supplments|title=Untested Stimulant Still in Dietary Supplements| vauthors = Goodman B |website=WebMD|date=7 April 2015}}</ref> This question was litigated during the trial of ''Hi Tech Pharmaceuticals Inc vs. Cohen''.<ref>{{cite journal | vauthors = Bagley N, Carroll AE, Cohen PA | title = Scientific Trials-In the Laboratories, Not the Courts | journal = JAMA Internal Medicine | volume = 178 | issue = 1 | pages = 7–8 | date = January 2018 | pmid = 29114742 | doi = 10.1001/jamainternmed.2017.5730 | url = http://nrs.harvard.edu/urn-3:HUL.InstRepos:34902783 }}</ref><ref>{{cite web|title=BMPEA and Acacia Rigidula: Hi-Tech Pharmaceuticals Fights Back|url=https://blog.priceplow.com/bmpea#natural|website=PricePlow|access-date=27 October 2015|date=26 October 2015}}</ref> Despite US Food and Drug Administration warning letters, BMPEA remains present in dietary supplements.<ref>{{cite journal | vauthors = Cohen PA, Wen A, Gerona R | title = Prohibited Stimulants in Dietary Supplements After Enforcement Action by the US Food and Drug Administration | journal = JAMA Internal Medicine | volume = 178 | issue = 12 | pages = 1721–1723 | date = December 2018 | pmid = 30422217 | pmc = 6583602 | doi = 10.1001/jamainternmed.2018.4846 }}</ref>

== Safety ==

β-Methylphenethylamine was associated with a case of cerebral hemorrhage in a Swedish athlete and first time user. The female victim with no medical history had taken a Swedish [[food supplement]] with 290&nbsp;mg β-methylphenethylamine per serving before commencing her usual exercises. After about 30 minutes the first symptoms appeared. The presence of the active ingredient was not declared on the label.<ref name = Cohen>{{cite journal | vauthors = Cohen PA, Zeijlon R, Nardin R, Keizers PH, Venhuis B | title = Hemorrhagic Stroke Probably Caused by Exercise Combined With a Sports Supplement Containing β-Methylphenyl-ethylamine (BMPEA): A Case Report | journal = Annals of Internal Medicine | volume = 162 | issue = 12 | pages = 879–880 | date = June 2015 | pmid = 26075771 | doi = 10.7326/L15-5101 | url = http://nrs.harvard.edu/urn-3:HUL.InstRepos:40997747 }}</ref> Use of β-Methylphenethylamine is also prohibited in sports.<ref name = Cholbinski>{{cite journal | vauthors = Chołbiński P, Wicka M, Kowalczyk K, Jarek A, Kaliszewski P, Pokrywka A, Bulska E, Kwiatkowska D | display-authors = 6 | title = Detection of β-methylphenethylamine, a novel doping substance, by means of UPLC/MS/MS | journal = Analytical and Bioanalytical Chemistry | volume = 406 | issue = 15 | pages = 3681–3688 | date = June 2014 | pmid = 24633566 | pmc = 4026626 | doi = 10.1007/s00216-014-7728-5 }}</ref>

* [[2-Phenyl-3-aminobutane|β-Methylamphetamine]]

{{Reflist}}

{{Monoamine releasing agents}}

{{TAAR ligands}}

[[Category:TAAR1 agonists]]

[[Category:Norepinephrine releasing agents]]