Human brain GABA levels rise after initiation of vigabatrin therapy but fail to rise further with increasing dose

被引：61
作者：
Petroff, OAC [1 ]
Rothman, DL [1 ]
Behar, KL [1 ]
Mattson, RH [1 ]
机构：
[1] YALE UNIV,DEPT MED,NEW HAVEN,CT 06510
来源：
NEUROLOGY | 1996年 / 46卷 / 05期
关键词：
D O I：
10.1212/WNL.46.5.1459
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
Using H-1 spectroscopy, we measured occipital lobe GABA levels serially in 18 patients enrolled in an ongoing open label trial of vigabatrin. Brain GABA levels were elevated twofold in patients taking vigabatrin (3 to 4 g/d) compared with nonepileptic subjects, Serial measurements suggested that brain GABA rose in proportion to vigabatpin dose up to 3 g/d. Doubling the dose from 3 to 6 g/d failed to increase brain GABA further. Serial measurements on three patients taking 6 g/d showed a gradual decrease in brain GABA in two patients over 1 to 2 years of treatment. These observations suggest that GABA synthesis may decrease at high GABA levels.
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收藏
页码：1459 / 1463
页数：5
相关论文
共 35 条
[1]   MEASUREMENT OF GABA FOLLOWING GABA-TRANSAMINASE INHIBITION BY GABACULINE - A H-1 AND P-31 NMR SPECTROSCOPIC STUDY OF RAT-BRAIN IN-VIVO [J].
BEHAR, KL ;
BOEHM, D .
MAGNETIC RESONANCE IN MEDICINE, 1994, 31 (06) :660-667
[2]   ANALYSIS OF MACROMOLECULE RESONANCES IN H-1-NMR SPECTRA OF HUMAN BRAIN [J].
BEHAR, KL ;
ROTHMAN, DL ;
SPENCER, DD ;
PETROFF, OAC .
MAGNETIC RESONANCE IN MEDICINE, 1994, 32 (03) :294-302
[3]   HIGH-RESOLUTION H-1 NUCLEAR MAGNETIC-RESONANCE STUDY OF CEREBRAL HYPOXIA INVIVO [J].
BEHAR, KL ;
DENHOLLANDER, JA ;
STROMSKI, ME ;
OGINO, T ;
SHULMAN, RG ;
PETROFF, OAC ;
PRICHARD, JW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (16) :4945-4948
[4]   EFFECT OF LONG-TERM VIGABATRIN THERAPY ON GABA AND OTHER AMINO-ACID-CONCENTRATIONS IN THE CENTRAL-NERVOUS-SYSTEM - A CASE-STUDY [J].
BENMENACHEM, E ;
HAMBERGER, A ;
MUMFORD, J .
EPILEPSY RESEARCH, 1993, 16 (03) :241-243
[5]   THE EFFECT OF DIFFERENT VIGABATRIN TREATMENT REGIMENS ON CSF BIOCHEMISTRY AND SEIZURE CONTROL IN EPILEPTIC PATIENTS [J].
BENMENACHEM, E ;
PERSSON, LI ;
SCHECHTER, PJ ;
HAEGELE, KD ;
HUEBERT, N ;
HARDENBERG, J ;
DAHLGREN, L ;
MUMFORD, JP .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1989, 27 :S79-S85
[6]   EFFECT OF LONG-TERM VIGABATRIN THERAPY ON SELECTED NEUROTRANSMITTER CONCENTRATIONS IN CEREBROSPINAL-FLUID [J].
BENMENACHEM, E ;
PERSSON, LI ;
MUMFORD, J ;
HAEGELE, KD ;
HUEBERT, N .
JOURNAL OF CHILD NEUROLOGY, 1991, 6 :S11-S16
[7]   IS THE ESTIMATION OF GABA TURNOVER RATE INVIVO A TOOL TO DIFFERENTIATE BETWEEN VARIOUS TYPES OF DRUGS INTERFERING WITH THE GABA BENZODIAZEPINE IONOPHORE RECEPTOR COMPLEX [J].
BERNASCONI, R ;
BITTIGER, H ;
SCHMUTZ, M ;
MARTIN, P ;
KLEIN, M .
NEUROPHARMACOLOGY, 1984, 23 (7B) :815-816
[8]   THE EFFECT OF VIGABATRIN ON BRAIN AND PLATELET GABA-TRANSAMINASE ACTIVITIES [J].
BOLTON, JB ;
RIMMER, E ;
WILLIAMS, J ;
RICHENS, A .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1989, 27 :S35-S42
[9]   VIGABATRIN FOR REFRACTORY COMPLEX PARTIAL SEIZURES - MULTICENTER SINGLE-BLIND STUDY WITH LONG-TERM FOLLOW-UP [J].
BROWNE, TR ;
MATTSON, RH ;
PENRY, JK ;
SMITH, DB ;
TREIMAN, DM ;
WILDER, BJ ;
BENMENACHEM, E ;
NAPOLIELLO, MJ ;
SHERRY, KM ;
SZABO, GK .
NEUROLOGY, 1987, 37 (02) :184-189
[10]   THE STRUCTURAL AND FUNCTIONAL-HETEROGENEITY OF GLUTAMIC-ACID DECARBOXYLASE - A REVIEW [J].
ERLANDER, MG ;
TOBIN, AJ .
NEUROCHEMICAL RESEARCH, 1991, 16 (03) :215-226
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