L-3,4-DIHYDROXYPHENYLALANINE METHYL ESTER HYDROCHLORIDE

Description

L-DOPA (Item No. 13248) is a metabolic precursor of dopamine that is capable of crossing the blood brain barrier to act as a dopamine D₁ receptor agonist. It is produced from L-tyrosine by trysosine hydroxylase. In the brain, L-DOPA is converted to dopamine by the enzyme aromatic L-amino acid decarboxylase. It is conventionally used to increase dopamine concentrations in the brain as a treatment for Parkinson’s disease and stroke recovery. L-DOPA methyl ester is a neutral derivative of L-DOPA formulated for increased solubility compared to the parent compound.

Chemical Properties

White Solid

Uses

L-3,4-Dihydroxyphenylalanine methyl ester hydrochloride has been used:

• in treating 6-hydroxydopamine induced lesions mice serotonin neurons
• in tyrosinase activity in B16F10 skin melanoma cells
• to test its neuroprotective effect in mesencephalic neurons

Uses

Precursor to L-DOPA that crosses the blood-brain barrier; antiparkinsonian agent.

Uses

Selective Dopamine D1 receptor agonist.

Biochem/physiol Actions

L-3,4-Dihydroxyphenylalanine methyl ester is a precursor to?L-DOPA that crosses the blood-brain barrier. Antiparkinsonian agent L-DOPA methyl ester elicits antitumor functionality in leukemia and melanoma.

Synthesis

67-56-1

59-92-7

1421-65-4

Methanol (50 mL) was cooled to -5°C in a thermostat bath and thionyl chloride (5 mL, 68.9 mmol) was added slowly and dropwise. Subsequently, 3,4-dihydroxy-L-phenylalanine (10.0 g, 50.7 mmol) was added in batches and the reaction mixture was stirred for 5 min after the addition was completed. The reaction system was gradually warmed up to room temperature and subsequently heated to 50 °C with continuous stirring for 14 hours. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure to afford methyl (S)-2-amino-3-(3,4-dihydroxyphenyl)propionate hydrochloride (14.3 g, 57.7 mmol, quantitative yield), the product was in the form of oil.1H-NMR (400 MHz, CD3OD) δ: 3.04 (dd, 1H, J = 7.4, 14.5 Hz), 3.13 (dd, 1H, J = 5.8, 14.5 Hz), 3.13 (dd, 1H, J = 5.8, 14.5 Hz). J = 5.8, 14.5 Hz), 3.84 (s, 3H), 4.22-4.25 (m, 1H), 6.58 (dd, 1H, J = 2.2, 8.0 Hz), 6.69 (d, 1H, J = 2.1 Hz), 6.77 (d, 1H, J = 8.0 Hz). esims (m/z): 212.7 ([M + H]+). 423.2 ([2M + H]+), 210.2 ([M - H]-), 241.1 ([M + Cl]-).

in vitro

l-dopa methyl ester is a neutral derivative of l-dopa formulated for increased solubility compared to the parent compound. l-dopa is a metabolic precursor of dopamine that is capable of crossing the blood brain barrier to act as a dopamine d1 receptor agonist [1].

in vivo

on intraperitoneal or subcutaneous administration to mice l-dopa methyl ester was found to be equivalent to l-dopa in reversing reserpine-induced akinesia and producing contraversive circling behaviour in rats. on oral administration the methyl ester was even more active. the administration of l-dopa or the methyl ester had equivalent changes of metabolite levels in striatal and mesolimbic dopamine, homovanillic acid, as well as 3,4-dihydroxyphenylacetic acid [2].

storage

-20°C

References

[1] berends, h. i.,nijlant, j.m.m.,movig, k.l.l., et al. the clinical use of drugs influencing neurotransmitters in the brain to promote motor recovery after stroke; a cochrane systematic review. european journal of physical and rehabilitation medicine 45(4), 621-630 (2009).
[2] cooper dr, marrel c, testa b, van de waterbeemd h, quinn n, jenner p, marsden cd. l-dopa methyl ester--a candidate for chronic systemic delivery of l-dopa in parkinson's disease. clin neuropharmacol. 1984;7(1):89-98.
[3] kleedorfer, b. ,lees, a.j. and stern, g.m. subcutaneous and sublingual levodopa methyl ester in parkinson’s disease. j.neurol.neurosurg.psychiatry 54(4), 373 (1991).