Abstract
Tetrahydroisoquinolines (TIQs) are intraneuronal, catecholamine-derived alkaloids that have been implicated in the etiology of Parkinson’s disease and in alcohol related disorders. The in vitro production of the cytotoxic hydroxyl radical (·OH) was recorded during the autoxidation of salsolinol (SAL) and salsolinol-1-carboxylic acid (SAL-1C), but not when these two catecholic TIQs were oxidized by tyrosinase. Significantly higher levels of the radical were produced when these catecholic TIQs were incubated with ·OH generating complexes, or with chelated iron. In contrast, mono-O-methylated TIQs such as salsoline (SLN) and salsoline-1-carboxylic acid (SLN-1C) did not generate ·OH during autoxidation or when incubated with chelated iron or tyrosinase. Radical production by ·OH-generating complexes was reduced in the presence of O-methylated TIQs. The neurotoxicity of TIQs may result from their propensity to autoxidize and generate reactive quinoids and ensuing oxygen radicals. The functional significance of the replacement of an hydroxyl group attached to C-7 of SAL or SAL-1C with a methoxyl group remains to be determined. This single structural modification may prevent mono-O-methylated TIQs from participating in catalytic redox cycling reactions that would otherwise augment ·OH production. If true, then O-methylation and other cellular mechanisms that circumvent the autoxidation of catecholamine-derived TIQs may reduce the likelihood of these substances forming cytotoxic quinoids and influencing endogenous ·OH-generating reactions.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsAuthor information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer Science+Business Media New York
About this chapter
Cite this chapter
Nappi, A.J., Vass, E., Collins, M.A. (2000). The Effects of Catecholic and O-Methylated Tetrahydroisoquinolines on the Production of Hydroxyl Radical. In: Storch, A., Collins, M.A. (eds) Neurotoxic Factors in Parkinson’s Disease and Related Disorders. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1269-1_43
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1269-1_43
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5470-3
Online ISBN: 978-1-4615-1269-1
eBook Packages: Springer Book Archive