Chemistry:Phenylalaninol
Phenylalaninol (code name PAL-329), or DL-phenylalaninol, also known as phenylmethylethanolamine or as α-(hydroxymethyl)phenethylamine, is a psychostimulant and monoamine releasing agent (MRA) of the phenethylamine family.[1][2] It is related to the amino acid phenylalanine and to the phenethylamine psychostimulants β-phenethylamine (phenylethylamine) and amphetamine (α-methylphenethylamine).[3]
Phenylalaninol is a psychostimulant and selective norepinephrine releasing agent (NRA) or norepinephrine-preferring norepinephrine–dopamine releasing agent (NDRA).[1][2] The EC50 values of phenylalaninol for monoamine release are 106 nM for norepinephrine, 1,355 nM for dopamine, and >10,000 nM for serotonin in rat brain synaptosomes.[1] It is dramatically less potent as an MRA than phenethylamine or amphetamine.[1][4] The potency of phenylalaninol in inducing norepinephrine release is 13-fold higher than its potency in inducing dopamine release.[1] Similarly to other dopamine releasers like amphetamine, the drug shows cocaine-like effects and reinforcing properties in rhesus monkeys.[1][2] The much greater potency of phenylalaninol in inducing norepinephrine over inducing dopamine release does not appear to interfere with its dopamine release-mediated reinforcing effects.[1][2]
The clinically used stimulant, wakefulness-promoting agent, and well-balanced norepinephrine–dopamine reuptake inhibitor (NDRI) solriamfetol (brand name Sunosi; O-carbamoyl-D-phenylalaninol) is a derivative of phenylalaninol with a carbamoyl substitution at the hydroxyl group of the molecule.[5] Phenylalaninol is a known impurity in chemical synthesis of solriamfetol.[6]
The predicted log P of phenylalaninol is 0.7 to 0.77 and hence it is relatively hydrophilic.[3][7] The compound appears to be actively transported in the body by some of the same transporters that transport phenylalanine, such as LAT3.[8][9]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Cocaine-like discriminative stimulus effects of "norepinephrine-preferring" monoamine releasers: time course and interaction studies in rhesus monkeys". Psychopharmacology 234 (23–24): 3455–3465. December 2017. doi:10.1007/s00213-017-4731-5. PMID 28889212.
- ↑ 2.0 2.1 2.2 2.3 "Intravenous Self-Administration of Synthetic Cathinones in Rhesus Monkeys". The FASEB Journal 32 (S1). 2018. doi:10.1096/fasebj.2018.32.1_supplement.550.3. ISSN 0892-6638.
- ↑ 3.0 3.1 "DL-Phenylalaninol". https://pubchem.ncbi.nlm.nih.gov/compound/76652.
- ↑ "Dopamine-releasing agents". Dopamine Transporters: Chemistry, Biology and Pharmacology. Hoboken [NJ]: Wiley. July 2008. pp. 305–320. ISBN 978-0-470-11790-3. OCLC 181862653. https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf.
- ↑ "Solriamfetol for the treatment of excessive daytime sleepiness associated with narcolepsy". Expert Rev Clin Pharmacol 12 (8): 723–728. August 2019. doi:10.1080/17512433.2019.1632705. PMID 31215815.
- ↑ "Enantioseparation of solriamfetol and its major impurity phenylalaninol by capillary electrophoresis using sulfated gamma cyclodextrin". Electrophoresis 42 (17–18): 1818–1825. September 2021. doi:10.1002/elps.202100076. PMID 34109644.
- ↑ "phenylalaninol". 10 June 2024. https://www.chemspider.com/Chemical-Structure.69116.html.
- ↑ "Inhibition of intestinal absorption of phenylalanine by phenylalaninol". J Biochem 78 (2): 269–275. August 1975. doi:10.1093/oxfordjournals.jbchem.a130904. PMID 1228171.
- ↑ "Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters". J Biol Chem 278 (44): 43838–45. October 2003. doi:10.1074/jbc.M305221200. PMID 12930836.
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