3 ‐ O ‐ methyldopa blocks dopa metabolism in rat corpus striatum

3 ‐ O ‐ methyldopa blocks dopa metabolism in rat corpus striatum 3‐O‐Methyldopa (OMD) given to rats inhibits striatal uptake and utilization of L‐dopa. Thus, the accumulation of L‐dopa, dopamine, 3,4‐dihydroxyphenylacetic acid, and homovanillic acid in OMD‐pretreated rats after L‐dopa injection is significantly lower compared with control rats. This effect of OMD is dose dependent. OMD inhibits L‐dopa accuumlation in the striatum after inhibition of aromatic amino acid decarboxylase activity with 3‐hydroxybenzylhydrazine‐HCL. This effect is not mediated through inhibition of firing in dopaminergic neurons, since the accumulation of dopamine in the striatum after γ‐butyrolactone injection was also significantly reduced by OMD. It is suggested that OMD competes with L‐dopa and tyrosine uptake into the brain. These findings are in line with clinical observations which indicate that high plasma levels of OMD in parkinsonian patients are associated with poor response to L‐dopa. The data presented here indicate that use of catechol‐O‐methyltransferase inhibitors with L‐dopa may be of value in the treatment of parkinsonian patients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Neurology Wiley

3 ‐ O ‐ methyldopa blocks dopa metabolism in rat corpus striatum

Annals of Neurology, Volume 12 (3) – Sep 1, 1982

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Publisher
Wiley
Copyright
Copyright © 1982 American Neurological Association
ISSN
0364-5134
eISSN
1531-8249
DOI
10.1002/ana.410120310
pmid
7137962
Publisher site
See Article on Publisher Site

Abstract

3‐O‐Methyldopa (OMD) given to rats inhibits striatal uptake and utilization of L‐dopa. Thus, the accumulation of L‐dopa, dopamine, 3,4‐dihydroxyphenylacetic acid, and homovanillic acid in OMD‐pretreated rats after L‐dopa injection is significantly lower compared with control rats. This effect of OMD is dose dependent. OMD inhibits L‐dopa accuumlation in the striatum after inhibition of aromatic amino acid decarboxylase activity with 3‐hydroxybenzylhydrazine‐HCL. This effect is not mediated through inhibition of firing in dopaminergic neurons, since the accumulation of dopamine in the striatum after γ‐butyrolactone injection was also significantly reduced by OMD. It is suggested that OMD competes with L‐dopa and tyrosine uptake into the brain. These findings are in line with clinical observations which indicate that high plasma levels of OMD in parkinsonian patients are associated with poor response to L‐dopa. The data presented here indicate that use of catechol‐O‐methyltransferase inhibitors with L‐dopa may be of value in the treatment of parkinsonian patients.

Journal

Annals of NeurologyWiley

Published: Sep 1, 1982

References

  • Barrier mechanisms for neurotransmitter monoamines and their precursors at the blood‐brain interface
    Hardebo, Hardebo; Owman, Owman

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