2,4,5-trihydroxyphenylalanine in solution forms a non-N-methyl-D-aspartate glutamatergic agonist and neurotoxin.
We have investigated the pharmacologic and neurotoxic properties of 2,4,5-trihydroxyphenylalanine [topa; the 6-hydroxylated derivative of 3,4-dihydroxyphenylalanine (dopa)] in central neurons. Application of solutions of topa to the chicken eyecup preparation results in glutamatergic responses mediated predominantly by non-N-methyl-D-aspartate receptors. Pharmacological activity depends upon oxidation in solution to a new compound. This compound is tentatively identified as topa quinone. Solutions of topa are toxic to cortical neurons in culture, and this toxicity is blocked by the non-N-methyl-D-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. These results suggest that production or accumulation of topa or its oxidation products might be involved in excitotoxicity, especially in dopaminergic neurons and their projection targets.
Rosenberg
P A
PA
Department of Neurology, Children's Hospital, Boston, MA.
Loring
R
R
Xie
Y
Y
Zaleskas
V
V
Aizenman
E
E
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology; D002645:Chickens; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000187:drug effects; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D009799:Ocular Physiological Phenomena; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats
D009498:Neurotoxins; D011810:Quinoxalines; C001388:6-hydroxydopa; D004295:Dihydroxyphenylalanine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione