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  • 1985-1989  (5)
  • 1
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 53 (1989), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Sprague-Dawley rats (200-260 g) were anesthetized with chJoral hydrate (400 mg/kg) and polyethylene cannulae were permanently implanted into the lateral ventricles. One or two days later, l-buthionine-[S,R]-sulfoximine (L-BSO), an apparently selective inhibitor of γ-glutamylcysteine synthetase, was administered intracerebroventricularly through the cannulae. The brain content of glutathione (GSH) was determined by HPLC with electrochemical detection (gold/ mercury electrode) using N-acetylcysteine as internal standard. A time-course study of the changes in the striatum following a single dose of l-BSO (3.2 mg) revealed a maximal depletion of GSH (-60%) approximately 48 h after the administration. The effects of various doses of l-BSO on GSH in the striatum, in the limbic region, and in the cortex were assessed at 24 h and 48 h after the administration. l-BSO (0.02-3.2 mg) produced dose-dependent reductions of GSH in all brain regions studied at both time intervals. In a long-term experiment l-BSO (3.2 mg) was administered every second day. After 4 days, i.e., after two injections, striatal GSH was reduced by approximately 70%. No further depletion of GSH was obtained by additional injections of l-BSO, but GSH was maintained at this low level for the 12 days studied. These results suggest that l-BSO, administered intracerebroventricularly, would serve as a useful tool for evaluation of the biological role of GSH in the CNS.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 52 (1989), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Sprague-Dawley rats were anesthetized with chloral hydrate, and plastic cannulae were permanently implanted into the lateral ventricles. The animals then were allowed to recover for 1–2 days. L-Buthionine sulfoximine (l-BSO), a selective inhibitor of glutathione (GSH) synthesis, and 6-hydroxydopamine (6-OH-DA), a selective catecholaminergic neurotoxin, were administered intracerebroventricularly. The striatal concentrations of GSH and monoamines were determined by HPLC with electrochemical detection. Two injections of l-BSO (3.2 mg, at a 48-h interval) resulted in a 70% reduction of striatal GSH. 6-OH-DA (150 or 300 μg) reduced the concentrations of striatal dopamine and noradrenaline 7 days after the administration, but left the concentrations of 5-hydroxytryptamine unaltered. L-BSO treatment did not produce any changes in the levels of monoamines per se but it potentiated the catecholamine-depleting effect of 6-OH-DA in the striatum. Thus, GSH appears to suppress the toxicity of 6-OH-DA, probably by scavenging the toxic species formed during 6-OH-DA oxidation. In view of these results one may suggest an important role for GSH in catecholaminergic neurons: protecting against the oxidation of endogenous catechols.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 234-245 
    ISSN: 1432-1912
    Keywords: Dopamine autoreceptors ; Dopamine antagonists ; 2-Aminotetralins ; Central stimulants ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The biochemical and behavioral effects of the putative dopamine autoreceptor antagonists cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76 and cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, were evaluated in various in vivo models in rats. Both compounds produced a marked elevation in brain dopamine synthesis and turnover with only slight effects on the synthesis and turnover of serotonin (5-HT) and noradrenaline being noted. (+)-AJ 76 and (+)-UH 232 also failed to antagonize the decrease in cortical noradrenaline synthesis rate caused by the alpha2 agonist clonidine. The apomorphine-induced decrease in dopamine synthesis rate in gamma-butyrolactone (GBL) treated animals was completely blocked by (+)-AJ 76 and (+)-UH 232 but not by d-amphetamine or methylphenidate. In activity experiments using habituated animals, (+)-AJ 76 and (+)-UH 232 produced locomotor stimulation and weak stereotypies and antagonized the sedative effects of low doses of apomorphine. Locomotor hyperactivity induced by apomorphine or the dopamine agonist DiPr-5,6-ADTN was antagonized by (+)-UH 232 and to a lesser degree by (+)-AJ 76. The locomotor hyperactivity produced by (+)-AJ 76, (+)-UH 232 and methylphenidate was completely prevented by reserpine pretreatment and partially blocked by the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (alpha-MT), whereas d-amphetamine-induced hyperactivity was only antagonized by alpha-MT pretreatment. It is concluded that (+)-AJ 76 and (+)-UH 232 produce behavioral stimulation via a preferential antagonism on central dopamine autoreceptors, an action different from that of all known stimulants including apomorphine, d-amphetamine and methylphenidate. (+)-AJ 76 and (+)-UH 232 possess but weak antagonistic effects on postsynaptic dopamine receptors and only the latter compound is able to induce sedation in rats.
    Type of Medium: Electronic Resource
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