2,4,5-Trihydroxyphenylalanine in Solution Forms a Non-N-Methyl-D- Aspartate Glutamatergic Agonist and Neurotoxin
Abstract
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.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- June 1991
- DOI:
- 10.1073/pnas.88.11.4865
- Bibcode:
- 1991PNAS...88.4865R