Effects of benserazide on L-DOPA-derived extracellular dopamine levels and aromatic L-amino acid decarboxylase activity in the striatum of 6-hydroxydopamine-lesioned rats.
Benserazide is commonly used for Parkinson's disease in combination with L-DOPA as a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor. However, recent studies using intact animals indicate that benserazide acts also in the central nervous system. We determined the influence of benserazide on the central AADC activity in rats with dopaminergic denervation and observed changes in extracellular dopamine (DA) levels after benserazide and L-DOPA administration. First, using in vivo microdialysis technique, we measured extracellular DA levels in the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rats treated with benserazide and L-DOPA. Second, we measured AADC activity in the striatal tissues after benserazide administration. Although administration of 5, 10 and 50 mg/kg benserazide to 6-OHDA-lesioned rats showed an identical increase in exogenous L-DOPA-derived extracellular DA levels, the time to reach the peak DA levels were significantly prolonged by benserazide dose-dependently. The AADC activity in the denervated striatal tissues showed a significant decrease by 10 mg/kg and 50 mg/kg benserazide. These results suggest that benserazide reduces the central AADC activity in the striatum of rats with nigrostriatal denervation, which leads to changes in the metabolism of exogenous L-DOPA. Central activity of AADC inhibitors should be taken into consideration when they are used both in experimental and clinical studies on Parkinson's disease.
Shen
Huo
H
Department of Neurological Science, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki 036-8216, Japan.
Kannari
Kazuya
K
Yamato
Hiroshi
H
Arai
Akira
A
Matsunaga
Muneo
M
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D001545:Benserazide / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D007980:Levodopa; D001545:Benserazide; D016627:Oxidopamine; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine