Summary.
The effects of the peripheral aromatic amino acid decarboxylase (AADC) inhibitors, carbidopa and benserazide, and the central AADC inhibitor, 3-hydroxybenzylhydrazine (NSD-1015) on peripheral and brain monoamine oxidase (MAO) A and B activity were investigated in the rat. In vitro, carbidopa, benserazide and NSD-1015 all potently inhibited hepatic MAO A and B activity (IC50 10–50 μM). In ex vivo studies following systemic drug administration, NSD-1015 (100 mg/kg ip) produced 88% and 96% inhibition of hepatic and striatal MAO A and B activity respectively. Carbidopa (12.5 mg/kg i.p.) and benserazide (50 mg/kg i.p.) had no effect on striatal MAO A activity or hepatic MAO B activity. However, they inhibited striatal MAO B activity by 45 ± 10% and 36 ± 10% respectively. In conclusion, carbidopa and benserazide may not only protect L-DOPA from peripheral decarboxylation, but also increase striatal dopamine content through MAO inhibition. NSD-1015 should not be used to investigate the neuromodulatory role of L-DOPA as it potently inhibits rat striatal MAO.
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Received March 8, 2002; accepted July 15, 2002 Published online November 22, 2002
Authors' address: Prof. P. Jenner, Neurodegenerative Disease Research Centre, Guy's, King's and St Thomas' School of Biomedical Sciences, King's College, London SE1 1UL, United Kingdom, e-mail: div.pharm@kcl.ac.uk
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Treseder, S., Rose, S., Summo, L. et al. Commonly used L-amino acid decarboxylase inhibitors block monoamine oxidase activity in the rat. J Neural Transm 110, 229–238 (2003). https://doi.org/10.1007/s00702-002-0778-4
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DOI: https://doi.org/10.1007/s00702-002-0778-4