Dopamine-depleting activity of L-3,4-(dioxyphenylacetyl)-phenylalanine

Dioxyphenylacetyl-L-DOPA was synthesized and shown to be resistant toward oxidative cyclization in the presence of plasma and brain extracts. This new DOPA derivative is slightly inhibitory towards monoamine oxidase (IC50 2.5 mM) and the synaptosomal uptake of dopamine (IC50 0.35 mM) and acts as an antagonist of haloperidol (IC50 0.6 microM) in displacing 3H-spiroperidol from isolated dopamine receptors. The substance, although more hydrophobic than DOPA, overcomes the blood-brain barrier to a lower extent than DOPA and lowers the levels of dopamine and norepinephrine in the left and right hemisphere of mice treated with it for 10 days at a dose of 10 mg/kg/day. Dioxyphenylacetyl-L-DOPA inhibits red cell hypotonic hemolysis and brain Na/K+-ATPase activity in vitro and potentiates the barbiturate-induced sleep.