Commonly used L-amino acid decarboxylase inhibitors block monoamine oxidase activity in the rat.
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 (IC(50) 10-50 micro M). 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.
Treseder
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Neurodegenerative Disease Research Centre, Guy's, King's and St Thomas' School of Biomedical Sciences, King's College, London, United Kingdom. div.pharm@kcl.ac.uk
Rose
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Summo
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Jenner
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D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006834:Hydrazines / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D006834:Hydrazines; D008996:Monoamine Oxidase Inhibitors; C004297:3-hydroxybenzylhydrazine; D008995:Monoamine Oxidase; D001142:Aromatic-L-Amino-Acid Decarboxylases