:Β-Methylphenethylamine

{{Drugbox

| verifiedrevid = 449584722

| IUPAC_name = 2-Phenylpropan-1-amine

| image = Beta-methylphenethylamine.png

| image2 = Beta-Methylphenethylamine molecule ball.png

| drug_name = β-Methylphenethylamine

| tradename =

| pregnancy_category =

| legal_status =

| legal_US = Unapproved "New Drug" (as defined by 21 U.S. Code § 321(p)(1)). Use in dietary supplements, food, or medicine is unlawful; otherwise uncontrolled.{{Cite web |date=February 22, 2023 |title=BMPEA in Dietary Supplements |url=https://www.fda.gov/food/dietary-supplement-ingredient-directory/bmpea-dietary-supplements |archive-url=https://web.archive.org/web/20230326151141/https://www.fda.gov/food/dietary-supplement-ingredient-directory/bmpea-dietary-supplements |url-status=dead |archive-date=26 March 2023 |access-date=June 9, 2023 |website=FDA}}

| routes_of_administration =

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

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

| CAS_number = 582-22-9

| ATC_prefix = none

| ATC_suffix =

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

| UNII = 6XL7O3V13L

| ChEMBL = 158578

| ChEBI = 229522

| PubChem = 11398

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 10920

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

| smiles = NCC(c1ccccc1)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C9H13N/c1-8(7-10)9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = AXORVIZLPOGIRG-UHFFFAOYSA-N

| 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.{{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 }} 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 (pressor) activity in experimental animals, and that it was orally active. The MLD (minimum lethal dose) for the HCl salt was given as 500 mg/kg (rat, s.c.) and 50 mg/kg (rabbit, i.v.).{{ 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 }}

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 mg/kg (rat, i.v.).{{ 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 }}

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. 123-124°.

Presence

In 2015, 52% of supplements labeled as containing Acacia rigidula were found to contain BMPEA.{{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 }}{{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 }} Consumers following recommended maximum daily servings would consume a maximum of 94 mg of BMPEA per day. In 2012, however, the FDA determined that BMPEA was not naturally present in Acacia rigidula leaves.{{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}} This question was litigated during the trial of Hi Tech Pharmaceuticals Inc vs. Cohen.{{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 | url-access = subscription }}{{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}} Despite US Food and Drug Administration warning letters, BMPEA remains present in dietary supplements.{{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 }}

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 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.{{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 | url-access = subscription }} Use of β-Methylphenethylamine is also prohibited in sports.{{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 }}

References

Category:Stimulants

Category:Phenethylamines

Category:TAAR1 agonists

Category:Norepinephrine releasing agents

:Β-Methylphenethylamine

Synthesis

Presence

Safety

See also

References