Review Article

Amino Acids

, Volume 14, Issue 1, pp 175-179

First online:

Destruction of catecholamine-containing neurons by 6-hydroxydopa, an endogenous amine oxidase cofactor

  • R. M. KostrzewaAffiliated withDepartment of Pharmacology, Quillen College of Medicine, East Tennessee State University
  • , R. BrusAffiliated withDepartment of Pharmacology, Silesian Academy of Medicine

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The amino acid, 6-hydroxydopa (6-OHDOPA), found at the active site of amine oxidases, exists as a keto-enol. Exogenously administered 6-OHDOPA is an excitotoxin likeβ-N-oxalylamino-L-alanine (BOAA) andβ-N-methylamino-L-alanine (BMAA), acting at the non-N-methyl-D-aspartate (non-NMDA)α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor. BMAA and BOAA are causal factors of neurolathyrism in humans. Much exogenously administered 6-OHDOPA is biotransformed by aminoacid decarboxylase (AADC) to the highly potent and catecholamine (CA) selective neurotoxin, 6-hydroxydopamine (6-OHDA). 6-OHDOPA destroys locus coeruleus noradrenergic perikarya and produces associated denervation of brain by norepinephrine-(NE) containing fibers. Opiopeptides and opioids enhance neurotoxic effects of 6-OHDOPA on noradrenergic nerves, by a naloxone-reversible process. An understanding of mechanisms underlying neurotoxic effects of 6-OHDOPA can be helpful in defining actions of known and newfound amino acids and for investigating their potential neurotoxic properties.


6-Hydroxydopa 6-Hydroxydopamine Noradrenergic neurons Neurotoxicity Excitatory amino acids