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.
Galzigna
L
L
Institute of Biological Chemistry, University of Padova, Italy.
Fasolato
C
C
Bianchi
M
M
Burlina
A P
AP
Previero
A
A
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007980:Levodopa / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects; D008995:Monoamine Oxidase / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000493:pharmacokinetics; D013574:Synaptosomes / Q000187:drug effects
D011954:Receptors, Dopamine; C059465:L-3,4-(dioxyphenylacetyl)phenylalanine; D007980:Levodopa; D013134:Spiperone; D008995:Monoamine Oxidase; D004298:Dopamine