Benserazide decreases central AADC activity, extracellular dopamine levels and levodopa decarboxylation in striatum of the rat

被引:47
作者
Jonkers, N
Sarre, S
Ebinger, G
Michotte, Y
机构
[1] Free Univ Brussels, Dept Pharmaceut Chem & Drug Anal, B-1090 Brussels, Belgium
[2] Univ Hosp, Dept Neurol, Brussels, Belgium
关键词
benserazide; carbidopa; aromatic amino acid decarboxylase; striatum; dopamine; microdialysis;
D O I
10.1007/s007020170056
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 l0mg/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 50mg/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.
引用
收藏
页码:559 / 570
页数:12
相关论文
共 23 条
[1]   EFFECTS OF L-DOPA ON EXTRACELLULAR DOPAMINE IN STRIATUM OF NORMAL AND 6-HYDROXYDOPAMINE-TREATED RATS [J].
ABERCROMBIE, ED ;
BONATZ, AE ;
ZIGMOND, MJ .
BRAIN RESEARCH, 1990, 525 (01) :36-44
[2]   EXTRACELLULAR CONCENTRATIONS OF DOPAMINE AND METABOLITES IN THE RAT CAUDATE AFTER ORAL-ADMINISTRATION OF A NOVEL CATECHOL-O-METHYLTRANSFERASE INHIBITOR RO 40-7592 [J].
ACQUAS, E ;
CARBONI, E ;
DEREE, RHA ;
DAPRADA, M ;
DICHIARA, G .
JOURNAL OF NEUROCHEMISTRY, 1992, 59 (01) :326-330
[3]   EFFECT OF VARIOUS DECARBOXYLASE INHIBITORS ON CEREBRAL METABOLISM OF DIHYDROXYPHENYLALANINE [J].
BARTHOLINI, G ;
PLETSCHER, A .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1969, 21 (05) :323-+
[4]   INCREASE OF CEREBRAL CATECHOLAMINES CAUSED BY 3,4-DIHYDROXYPHENYLALANINE AFTER INHIBITION OF PERIPHERAL DECARBOXYLASE [J].
BARTHOLINI, G ;
BURKARD, WP ;
PLETSCHER, A ;
BATES, HM .
NATURE, 1967, 215 (5103) :852-+
[5]   MICRODIALYSIS - THEORY AND APPLICATION [J].
BENVENISTE, H ;
HUTTEMEIER, PC .
PROGRESS IN NEUROBIOLOGY, 1990, 35 (03) :195-215
[6]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[7]   INTRACEREBRAL DIALYSIS MONITORING OF STRIATAL DOPAMINE RELEASE AND METABOLISM IN RESPONSE TO L-DOPA [J].
BRANNAN, T ;
KNOTT, P ;
KAUFMANN, H ;
LEUNG, L ;
YAHR, M .
JOURNAL OF NEURAL TRANSMISSION, 1989, 75 (02) :149-157
[8]   EFFECTS OF DECARBOXYLASE INHIBITION ON THE BIOSYNTHESIS OF BRAIN MONOAMINES [J].
BRODIE, BB ;
KUNTZMAN, R ;
HIRSCH, CW ;
COSTA, E .
LIFE SCIENCES, 1962, (03) :81-84
[9]   COMPARISON OF EFFECTS OF L-DOPA, AMPHETAMINE AND APOMORPHINE ON FIRING RATE OF RAT DOPAMINERGIC NEURONS [J].
BUNNEY, BS ;
AGHAJANIAN, GK ;
ROTH, RH .
NATURE-NEW BIOLOGY, 1973, 245 (143) :123-125
[10]   Effect of L-dopa alone and with benserazide on the spontaneous activity of striatal neurones in normal and 6-hydroxydopamine-lesioned rats [J].
Chang, WY ;
Webster, RA .
BRITISH JOURNAL OF PHARMACOLOGY, 1997, 121 (02) :331-337