Benserazide decreases central AADC activity, extracellular dopamine levels and levodopa decarboxylation in striatum of the rat.
In Parkinsonian patients treated with levodopa, peripheral decarboxylase inhibitors like carbidopa and benserazide are used to increase the central availability of levodopa. In experimental animal studies, this clinical situation is mimicked. However, at the dose used in many animal studies, both benserazide and carbidopa pass the blood brain barrier. In this study, we investigated to what extent their presence in brain inhibits striatal aromatic amino acid decarboxylase activity. At 50 mg/kg i.p., both carbidopa and benserazide decreased striatal decarboxylase activity. At 10 mg/kg i.p., only benserazide decreased the enzyme activity, but this did not change extracellular dopamine in striatum and allowed dopamine levels to increase after levodopa administration. In contrast, the inhibition of central decarboxylase activity by 50 mg/kg benserazide decreased striatal dopamine levels and prevented the levodopa-induced increase. Therefore, it is important to carefully consider the dose of the peripheral decarboxylase inhibitor used when the central effects of levodopa are studied.
Jonkers
N
N
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels, Belgium.
Sarre
S
S
Ebinger
G
G
Michotte
Y
Y
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001545:Benserazide / Q000494:pharmacology*; D002230:Carbidopa / Q000494:pharmacology; D003653:Decarboxylation / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects* / Q000201:enzymology; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D015259:Dopamine Agents; D007980:Levodopa; D001545:Benserazide; D001142:Aromatic-L-Amino-Acid Decarboxylases; D002230:Carbidopa; D004298:Dopamine