Α-Methylphenylalanine

{{Short description|Monoamine metabolism inhibitor}}

{{DISPLAYTITLE:α-Methylphenylalanine}}

{{Distinguish|AMPA}}

{{Drugbox

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| drug_name = α-Methylphenylalanine

| image = α-Methylphenylalanine.svg

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| class = Tyrosine hydroxylase inhibitor; Phenylalanine hydroxylase inhibitor; Catecholamine depleting agent; Catecholamine releasing agent

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| CAS_number_Ref =

| CAS_number = 23239-35-2

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| PubChem = 2724754

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| ChemSpiderID = 2006873

| UNII = W4V7K5BM5T

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| ChEBI = 141138

| ChEMBL = 4249392

| synonyms = α-MePhe; α-Me-Phe; α-Methyl-Phe; AMPA; α-Methyl-L-Phenylalanine

| IUPAC_name = (2S)-2-amino-2-methyl-3-phenylpropanoic acid

| C=10 | H=13 | N=1 | O=2

| SMILES = C[C@](CC1=CC=CC=C1)(C(=O)O)N

| StdInChI_Ref =

| StdInChI = 1S/C10H13NO2/c1-10(11,9(12)13)7-8-5-3-2-4-6-8/h2-6H,7,11H2,1H3,(H,12,13)/t10-/m0/s1

| StdInChIKey_Ref =

| StdInChIKey = HYOWVAAEQCNGLE-JTQLQIEISA-N

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α-Methylphenylalanine (α-MePhe or AMPA) is an artificial amino acid and a phenethylamine and amphetamine derivative.{{Cite web |title=alpha-methyl-L-phenylalanine |url=https://pubchem.ncbi.nlm.nih.gov/compound/2724754 |access-date=8 October 2024 |website=PubChem}} It is the α-methylated analogue of phenylalanine, the precursor of the catecholamine neurotransmitters, and the amino acid analogue of amphetamine (α-methylphenethylamine), a psychostimulant and monoamine releasing agent.

α-MePhe is a tyrosine hydroxylase inhibitor, thereby preventing the transformation of tyrosine into L-DOPA, and results in depletion of the catecholamine neurotransmitters.{{Cite journal |vauthors=Torchiana ML, Porter CC, Stone CA, Hanson HM |date=May 1970 |title=Some biochemical and pharmacological actions of α-methylphenylalanine |journal=Biochem Pharmacol |volume=19 |issue=5 |pages=1601–1614 |doi=10.1016/0006-2952(70)90148-6 |pmid=4998458}} It is also an inhibitor of phenylalanine hydroxylase, and in conjunction with phenylalanine administration, induces hyperphenylalaninemia analogous to that in phenylketonuria in animals.{{Cite journal |vauthors=Wyse AT, Dos Santos TM, Seminotti B, Leipnitz G |date=June 2021 |title=Insights from Animal Models on the Pathophysiology of Hyperphenylalaninemia: Role of Mitochondrial Dysfunction, Oxidative Stress and Inflammation |journal=Mol Neurobiol |volume=58 |issue=6 |pages=2897–2909 |doi=10.1007/s12035-021-02304-1 |pmid=33550493}}{{Cite journal |vauthors=Alexander SP, Fabbro D, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA |date=December 2019 |title=THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Enzymes |journal=Br J Pharmacol |volume=176 Suppl 1 |issue=Suppl 1 |pages=S297–S396 |doi=10.1111/bph.14752 |pmc=6844577 |pmid=31710714}}{{Cite journal |vauthors=Benevenga NJ, Steele RD |date=1984 |title=Adverse effects of excessive consumption of amino acids |journal=Annu Rev Nutr |volume=4 |pages=157–181 |doi=10.1146/annurev.nu.04.070184.001105 |pmid=6235826}}{{Cite journal |vauthors=Greengard O, Yoss MS, Del Valle JA |date=June 1976 |title=Alpha-methylphenylalanine, a new inducer of chronic hyperphenylalaninemia in sucling rats |journal=Science |volume=192 |issue=4243 |pages=1007–1008 |doi=10.1126/science.944951 |pmid=944951}}{{Cite journal |vauthors=Huether G, Neuhoff V |date=1981 |title=Use of alpha-methylphenylalanine for studies of brain development in experimental phenylketonuria |journal=J Inherit Metab Dis |volume=4 |issue=2 |pages=67–68 |doi=10.1007/BF02263594 |pmid=6790851}} The drug is known to produce metaraminol (3,β-dihydroxyamphetamine), a catecholamine releasing agent, as an active metabolite in animals, and this metabolite contributes to its effects.{{Cite journal |vauthors=Bollinger FW |date=April 1971 |title=Resolution of DL-alpha-methylphenylalanine |journal=J Med Chem |volume=14 |issue=4 |pages=373–375 |doi=10.1021/jm00286a028 |pmid=5553758}}

α-MePhe is a substrate of the L-type amino acid transporter 1 (LAT1), which transports it across the blood–brain barrier into the central nervous system.{{Cite journal |vauthors=Zhang J, Xu Y, Li D, Fu L, Zhang X, Bao Y, Zheng L |date=2020 |title=Review of the Correlation of LAT1 With Diseases: Mechanism and Treatment |journal=Front Chem |volume=8 |pages=564809 |doi=10.3389/fchem.2020.564809 |pmc=7606929 |pmid=33195053 |doi-access=free}}{{Cite journal |vauthors=Chen S, Jin C, Ohgaki R, Xu M, Okanishi H, Kanai Y |date=February 2024 |title=Structure-activity characteristics of phenylalanine analogs selectively transported by L-type amino acid transporter 1 (LAT1) |journal=Sci Rep |volume=14 |issue=1 |pages=4651 |doi=10.1038/s41598-024-55252-w |pmc=10897196 |pmid=38409393}}