Commonly used L-amino acid decarboxylase inhibitors block monoamine oxidase activity in the rat

被引:19
作者
Treseder, SA [1 ]
Rose, S [1 ]
Summo, L [1 ]
Jenner, P [1 ]
机构
[1] Kings Coll London, Guys Kings & St Thomas Sch Biomed Sci, Neurodegenerat Dis Res Ctr, London SE1 1UL, England
关键词
monoamine oxidase; L-amino acid decarboxylase; striatum; carbidopa; benserazide; NSD-1015;
D O I
10.1007/s00702-002-0778-4
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 (IC50 10-50 muM). 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.
引用
收藏
页码:229 / 238
页数:10
相关论文
共 31 条
[1]   L-DOPA STIMULATES THE RELEASE OF [H-3] GAMMA-AMINOBUTYRIC-ACID IN THE BASAL GANGLIA OF 6-HYDROXYDOPAMINE LESIONED RATS [J].
ACEVES, J ;
FLORAN, B ;
MARTINEZFONG, D ;
SIERRA, A ;
HERNANDEZ, S ;
MARISCAL, S .
NEUROSCIENCE LETTERS, 1991, 121 (1-2) :223-226
[2]   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-+
[3]   INHIBITION OF DECARBOXYLASE OF AROMATIC AMINO ACIDS BY 2,3,4-TRIHYDROXYBENZYLHYDRAZINE + ITS SERYL DERIVATIVE [J].
BURKARD, WP ;
PLETSCHER, A ;
GEY, KF .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1964, 107 (02) :187-&
[4]  
CARLSSON A, 1972, PHARMACOL REV, V24, P371
[5]   THE AROMATIC AMINO-ACID DECARBOXYLASE INHIBITOR, NSD-1015, INCREASES RELEASE OF DOPAMINE - RESPONSE CHARACTERISTICS [J].
DLUZEN, D ;
REDDY, A ;
MCDERMOTT, J .
NEUROPHARMACOLOGY, 1992, 31 (12) :1223-1229
[6]  
FINBERG JPM, 1995, J NEUROCHEM, V65, P1213
[7]   THE NATURE OF THE SUBSTRATE-SELECTIVE INTERACTION BETWEEN RAT-LIVER MITOCHONDRIAL MONOAMINE-OXIDASE AND OXYGEN [J].
FOWLER, CJ ;
ORELAND, L .
BIOCHEMICAL PHARMACOLOGY, 1980, 29 (16) :2225-2233
[8]   THE METABOLISM OF DOPAMINE BY BOTH FORMS OF MONOAMINE-OXIDASE IN THE RAT-BRAIN AND ITS INHIBITION BY CIMOXATONE [J].
FOWLER, CJ ;
BENEDETTI, MS .
JOURNAL OF NEUROCHEMISTRY, 1983, 40 (06) :1534-1541
[9]   L-DOPA INDUCES CA2+-DEPENDENT AND TETRODOTOXIN-SENSITIVE RELEASE OF ENDOGENOUS GLUTAMATE FROM RAT STRIATAL SLICES [J].
GOSHIMA, Y ;
OHNO, K ;
NAKAMURA, S ;
MIYAMAE, T ;
MISU, Y ;
AKAIKE, A .
BRAIN RESEARCH, 1993, 617 (01) :167-170
[10]   L-DOPA METHYL-ESTER ANTAGONIZES COMPETITIVELY L-DOPA-INDUCED FACILITATION OF NORADRENALINE RELEASE FROM RAT HYPOTHALAMIC SLICES [J].
GOSHIMA, Y ;
NAKAMURA, S ;
MISU, Y .
JAPANESE JOURNAL OF PHARMACOLOGY, 1990, 52 (01) :174-177