This is a really interesting article by Panneton et al. investigating the endogenous metabolite of dopamine, DOPAL. DOPAL was shown to be a selective toxin to nigral neurones. This raised the question if other toxic metabolites have been investigated. It is often overlooked that there is evidence that 6-hydroxydopamine (6-OHDA) is produced by the breakdown of dopamine [1] and L-Dopa [2,3]. It is also interesting to note that 6-OHDA has been detected in the urine of Parkinsonian patients treated with L-Dopa [4]. Could 6-OHDA been the first toxic metabolite investigated in vivo?
Another really important feature of this very careful study by Panneton et al. is the observation that the toxin not only kills neurones but it also decreased the expression of tyrosine hydroxylase in surviving neurones. This increase in non-TH neurones is also a common feature with 6-OHDA lesions [5].

1. Napolitano, A. et al. New Reaction Pathways of Dopamine under Oxidative Stress Conditions: Nonenzymatic Iron-Assisted Conversion to Norepinephrine and the Neurotoxins 6-Hydroxydopamine and 6,7-Dihydroxytetrahydroisoquinoline, Chem. Res. Toxicol. 1999, 12, 1090-1097
2. Maharaj, H. et al. l-DOPA administration enhances 6-hydroxydopamine generation Brain Research 1063 (2005) 180 – 186
3. Borah, A. L-DOPA-induced 6-hydroxydopamine production in the striata of rodents is sensitive to the degree of denervation. Neurochemistry International 56 (2010)
4. Andrew R, et al. The determination of hydroxydopamines and other trace amines in the urine of parkinsonian patients and normal controls. Neurochem Res 1993; 18:1175–1177
5. Finkelstein, D.I., et al. Axonal sprouting following lesions of the rat substantia nigra, Neuroscience, 2000. 97(1): p. 99-112.