Amantadine increases L-DOPA-derived extracellular dopamine in the striatum of 6-hydroxydopamine-lesioned rats.
We investigated the effect of amantadine on L-DOPA-derived extracellular dopamine (DA) levels and aromatic L-amino acid decarboxylase (AADC) activity in the striatum of rats with nigrostriatal dopaminergic denervation by 6-hydroxydopamine (6-OHDA). Pretreatment with 30 mg/kg amantadine increased the cumulative amount of extracellular DA in the striatum of 6-OHDA-lesioned rats treated with 10 mg/kg benserazide and 50 mg/kg L-DOPA to 250% of that without amantadine (P<0.01). Under pretreatment with 10 mg/kg benserazide, AADC activity after 30 mg/kg amantadine administration was reduced to 43% of controls (P<0.01). Amantadine-induced increase in L-DOPA-derived extracellular DA provides the basis for the clinical usefulness of amantadine in combination with L-DOPA. However, the effect of amantadine on L-DOPA-derived extracellular DA may not be caused by changes in AADC activity.
Arai
Akira
A
Department of Neurological Science, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8216, Japan.
Kannari
Kazuya
K
Shen
Huo
H
Maeda
Tetsuya
T
Suda
Toshihiro
T
Matsunaga
Muneo
M
D018663:Adrenergic Agents / Q000633:toxicity; D000547:Amantadine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001545:Benserazide / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D007980:Levodopa / Q000378:metabolism; D008297:Male; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018663:Adrenergic Agents; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D007980:Levodopa; D001545:Benserazide; D016627:Oxidopamine; D000547:Amantadine; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine