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  • 1
    Electronic Resource
    Electronic Resource
    Neurochemical and Neuroprotective Effects of Some Aliphatic Propargylamines: New Selective Nonamphetamine-Like Monoamine Oxidase B Inhibitors (1994)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 62 (1994), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Aliphatic N-propargylamines have recently been discovered to be highly potent, selective, and irreversible monoamine oxidase B (MAO-B) inhibitors. N-Methyl-N-(2-pentyl)propargylamine (M-2-PP) and N-methyl-N-(2-hexyl) propargylamine (2-HxMP), for example, are approximately fivefold more potent than I-deprenyl at inhibiting mouse brain MAO-B activity following oral administration. These inhibitors are nonaromatic compounds and are chemically quite different from other known MAO-B inhibitors. Some of their neurochemical and neuroprotective properties have been evaluated and compared with those of I-deprenyl. We have confirmed that these new inhibitors selectively inhibit MAO-B activity both in vitro and in vivo. 2-Phenylethylamine levels were substantially increased following administration of M-2-PP, but the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid were not affected except at high, nonselective doses. Chronic oral administration of I-deprenyl and M-2-PP causes selective inhibition of MAO-B activity and increases dopamine levels in mouse caudate. M-2-PP, like I-deprenyl, has been shown to be potent in protecting against MPTP-induced damage in the mouse. N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenaline neurotoxin, is not an MAO substrate. Its noradrenaline-depleting effects were substantially mitigated by I-deprenyl as well as by M-2-PP and 2-HxMP in the mouse hippocampus. Administration of 2-phenylethylamine, however, failed to reverse the effect of DSP-4. The neuroprotective effect of M-2-PP and 2-HxMP is apparently unrelated to the uptake of DSP-4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1994.62020697.x
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  • 2
    Electronic Resource
    Electronic Resource
    Deuterium Isotope Effect in γ-Aminobutyric Acid Transamination: Determination of Rate-Limiting Step (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 48 (1987), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The rate of transamination of γ-aminobutyric acid (GABA) catalyzed by hog brain γ-aminobutyrate ami-notransferase was substantially reduced when the hydrogen at the γ-carbon position was replaced by deuterium. The deuterium isotope effect of this reaction has been substantiated by fluorometric, radiometric, and mass spectrometric procedures and assessed kinetically. The ratios of Vmax of the nonlabeled substrate/Vmax of the deuterated substrate obtained under different conditions ranged from 6 to 7. This indicates that the cleavage of the hydrogen from the γ-carbon is the rate-determining step in GABA transamination. Similar isotope effects have also been shown to occur in the peripheral system in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1987.tb04112.x
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  • 3
    Electronic Resource
    Electronic Resource
    NET PRODUCTION OF γ-AMINOBUTYRIC ACID IN ASTROCYTES IN PRIMARY CULTURES DETERMINED BY A SENSITIVE MASS SPECTROMETRIC METHOD (1979)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 32 (1979), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A sensitive and specific high resolution mass spectrometric method, using a deuterium labelled internal standard, was developed for the quantitation of GABA in biological materials. GABA was converted to the DNS-γ-butyrolactam, isolated by thin layer chromatography and quantitated by the integrated ion current procedure. The method was used to measure the GABA content of cultured astrocytes (0.0545 nmol/mg protein, depending upon the culturing conditions), of fresh media (0.02–0.04 μM) and of conditioned media (after culturing in the absence of added GABA: 0.02–1.8 μM, depending upon the culturing conditions). An estimate of the rate of GABA production was obtained from the concentration in conditioned media and in the cells when GABA degradation was inhibited by AOAA (13 μM). The production of GABA was negligible in the cells grown under ordinary conditions but increased to 0.3 nmol/h per mg protein in cells which had been grown in the presence of 0.25 mM- dibutyryl cyclic AMP for 1 week. This value is of the same order of magnitude as the GAD activity observed in extraneurónal tissue. However, the GABA production measured mass spectrometrically was much lower than that of labelled GABA from [U-14C]glutamate. The latter value was non-reproducible and varied from one batch of radioactive glutamate to another.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1979.tb00361.x
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of chronic deuterated and non-deuterated phenelzine on rat brain monoamines and monoamine oxidase (1988)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 279-283 
    Details
    ISSN: 1432-1912
    Keywords: Chronic administration ; Phenelzine ; Deuterium substitution ; Monoamines ; Monoamine oxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of phenelzine and 1,1-dideuterophenelzine (0.5 or 2.5 mg/kg/day) administered s.c. via miniosmotic pumps for 13 days were compared. Striatal levels of p-tryrosine and tryptophan were unaffected by either treatment. The concentrations of DOPAC, HVA and 5-HIAA were dose-dependently decreased by phenelzine and deuterated phenelzine; furthermore, the deuterated compound decreased the amounts of these acids more than the same dose of phenelzine. Dopamine levels were increased by a rather small amount by all drug treatments; no effects of drug dose or drug type (deuterated or nondeuterated) were observed. With the exception of phenylethylamine, qualitatively similar effects were found with all other amines measured; their amounts were increased dose-dependently and the effects of deuterated phenelzine were greater than those of phenelzine. Rat cerebral MAO activity was inhibited dose-dependently by phenelzine and by deuterated phenelzine. Type A MAO was inhibited more than type B, and deuterated phenelzine inhibited both types more than did phenelzine. The present study shows that the efficacy of phenelzine was increased about 5-fold by deuteration, that deuterated phenelzine increased tryptamine, m-tyramine and p-tyramine levels much more than it did the other monoamines, that phenylethylamine levels were least affected by the drug treatments, and that deuterated phenelzine inhibited MAO more than did phenelzine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168839
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  • 5
    Electronic Resource
    Electronic Resource
    Inhibition of MAO-B by (−)-deprenyl alters dopamine metabolism in the macaque (Macaca facicularis) brain (1995)
    Springer
    Neurochemical research 20 (1995), S. 1503-1510 
    Details
    ISSN: 1573-6903
    Keywords: Monoamine oxidase ; dopamine ; phenylethylamine ; primate brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study has examined whether MAO-B has a role in DA metabolism in the primate CNS in situ. Eleven macaques (macaca facicularis) were used in this study to examine the effects of (-)-deprenyl (1 mg/kg, i.v., 2 and 24 hours). (-)-Deprenyl administration completely and selectively blocked MAO-B activity and blocked DA metabolism in the caudate nucleus and frontal cortex. DA metabolism in the substantia nigra was not affected by MAO-B inhibition. Changes in DA metabolism were accompanied by changes in 5-hydroxytryptamine (5HT) turnover: 5-hydroxyindole acetic acid (5HIAA) levels increased in the caudate and decreased in the frontal cortex. Levels of 2-phenylethylamine (PE), a putative modulator of dopaminergic transmission, were increased by MAO-B inhibition in all three brain regions examined. It is concluded that in some regions of the primate brain, in contrast to the rat, MAO-B has an important role in DA metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00970600
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of nutritional stress on brain tyramine concentration and dopamine turnover (1988)
    Springer
    Neurochemical research 13 (1988), S. 567-570 
    Details
    ISSN: 1573-6903
    Keywords: p-Tyramine ; m-tyramine ; dopamine concentration ; dopamine turnover ; nutritional stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This is an investigation of the effect of nutritional stress at various ages on the levels of thep- andm-isomers of tyramine in the caudate nucleus of the rat. For comparison, the effects of nutritional stress on the concentration and turnover of dopamine were also studied. Nutritional stress induced in pre-weaning (3 weeks of age) or post-weaning (up to 9 weeks of age) rats resulted in a decrease in the concentration ofp-tyramine and an increase in the concentration ofm-tyramine in the caudate nucleus. Dopamine concentration or turnover in the caudate nucleus was not affected by pre-weaning undernutrition; in the olfactory tubercles, however, a significant decrease was observed in dopamine turnover, calculated from the decrease in homovanillic acid levels after monoamine oxidase inhibition. The results suggest the changes observed are dependent on the availability of the amino acid precursorsp- andm-tyrosine and their competition towards aromatic-l-amino acid decarboxylase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00973299
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  • 7
    Electronic Resource
    Electronic Resource
    Determination of regional distributions of phenylethylamine andmeta-andpara-tyramine in rat brain regions and presence in human and dog plasma by an ultra-sensitive negative chemical ion gas chromatography-mass spectrometric (NCI-GC-MS) method (1993)
    Springer
    Neurochemical research 18 (1993), S. 995-1002 
    Details
    ISSN: 1573-6903
    Keywords: Phenylethylamine ; tyramine ; biogenic amines ; rat brain ; human plasma ; mass spectrometry ; negative ion ; GC-MS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using a new ultrasensitive method the trace biogenic amines, phenylethylamine,meta-tyramine andpara-tyramine have been quantitated in brain regions obtained from a single rat. Phenylethylamine concentrations in ng/g wet tissue (mean±std. error) were as follows: caudate 2.71±0.73, hypothalamus 0.45±0.15, cerebellum 0.09±0.02, olfactory bulb 0.35±0.11, stem 0.13±0.03, hippocampus 0.20±0.11, cortex 0.69±0.13 and the rest (remainder of the brain) 2.81±0.41. Mean whole brain was 1.23±0.19 ng/g, in agreement with previous measurements.meta-Tyramine concentrations (ng/g) were: caudate 2.69±0.19, hypothalamus 0.32±0.16, cerebellum 0.07±0.04, olfactory bulb 0.09±0.04, stem 0.04±0.01, hippocampus, 0.07±0.02, cortex 0.18±0.15 and the rest 0.15±0.06, with a mean whole brain value of 0.26±0.05 ng/g andpara-tyramine concentrations were: caudate 8.99±1.60, hypothalamus 0.93±0.13, cerebellum 0.78±0.27, olfactory bulb 0.70±0.13, stem 0.90±0.36, hippocampus 0.40±0.06, cortex 1.78±0.28 and the rest 2.38±0.12 and mean whole brain was 1.90±0.25 ng/g. In human plasma the concentrations of the three amines were found to be 31.3±3.4 pg/ml, 5.3±1.6 pg/ml and 66.0±9.9 pg/ml respectively and in dog blood 95.3±4.6 pg/ml, 24.0±7.6 pg/ml and 486±43 pg/ml respectively. When monoamine oxidase inhibitors were added to the blood immediately after collection there were no significant increases in the amine levels indicating that MAO-B is not present in plasma in significant quantities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00966759
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  • 8
    Electronic Resource
    Electronic Resource
    The effect ofl-deprenyl on behavior, cognitive function, and biogenic amines in the dog (1993)
    Springer
    Neurochemical research 18 (1993), S. 1211-1219 
    Details
    ISSN: 1573-6903
    Keywords: l-Deprenyl ; monoamine oxidase ; dopamine ; cognitive function ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Behavioral and pharmacological effects of oral administration ofl-deprenyl in the dog are described. Spontaneous behavior is unaffected at doses below 3 mg/kg while at higher doses there was stereotypical responding. There was evidence of improved cognitive function in animals chronically treated with a 1 mg/kg dose but the effectiveness varied considerably between subjects. Chronic administration produced a dose dependent inhibition in brain, kidney and liver monoamine oxidase B, and had no effect on monoamine oxidase A. There were also dose dependent increases in brain phenylethylamine and in plasma levels of amphetamine. Dog platelets did not have significant levels of MAO-B. Brain dopamine and serotonin metabolism were unaffected byl-deprenyl at doses up to 1 mg/kg. It appears that for the dog, deamination of catecholamines is controlled by MAO-A. Nevertheless, it is suggested thatl-deprenyl serves as a dopaminergic agonist, and there is also evidence that it affects adrenergic transmission. These catecholaminergic actions may account for the effects ofl-deprenyl on behavior and cognitive function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00975038
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  • 9
    Electronic Resource
    Electronic Resource
    High-performance liquid chromatographic analysis of monoamines and some of theirγ-glutamyl conjugates produced by the brain and other tissues ofHelix aspersa (gastropoda) (1990)
    Springer
    Cellular and molecular neurobiology 10 (1990), S. 175-192 
    Details
    ISSN: 1573-6830
    Keywords: norepinephrine ; dopamine ; 5-hydroxytryptamine ; Helix aspersa ; snail ; monoamine catabolism ; γ-glutamyl conjugation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary 1. Earlier reports from this and other laboratories have indicated that wide variations exist in estimates of the concentrations of norepinephrine in the brain and heart of the snailHelix aspersa. This is a report on investigations of norepinephrine concentrations inHelix aspersa tissues using high-performance liquid chromatography with electrochemical detection. In addition, the effects of treatment with some amino acid precursors or enzyme inhibitors on the concentrations of norepinephrine, dopamine, 5-hydroxytryptamine, and some of their metabolites were investigated. 2. The levels of norepinephrine in the brain were low (46 ng/g) in comparison to dopamine (2.1)εg/g) and 5-hydroxytryptamine (2.6εg/g). Epinephrine was not observed in either snail heart of snail nervous tissue. 3. Administration ofl-3,4-dihydroxyphenylalanine resulted in elevated snail brain dopamine, while 3,4-dihydroxyphenylserine treatment increased norepinephrine. Treatment with blockers of tyrosine hydroxylase and aromatic-l-amino acid decarboxylase reduced dopamine concentrations without affecting 5-hydroxytryptamine. 4. The dopamine metabolite 3,4-dihydroxyphenylacetic acid was observed only after administration ofl-3,4-dihydroxyphenylalanine or dopamine and then only in very small amounts. At no time was the dopamine metabolite homovanillic acid or the 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid observed in brain, heart, or whole-body extracts of the snail. 5. Incubation of nervous tissue with either dopamine or 5-hydroxytryptamine resulted in the production of electrochemically active metabolites which were identified by oxidation characteristics and cochromatography with synthesized standards as theγ-glutamyl conjugates of the amines. Treatment of snails with 5-hydroxytryptamine or dopamine also resulted in the production ofγ-glutamyl conjugates. 6. The present experiments show that great care must be exercised when measuring monoamines and their metabolites in gastropod tissues by highperformance liquid chromatography with electrochemical detection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00734572
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  • 10
    Electronic Resource
    Electronic Resource
    Qualitative and quantitative mass spectrometry of some noncatecholic biogenic amines and related compounds as their dansyl derivatives (1974)
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 1 (1974), S. 83-95 
    Details
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The use of the integrated ion current technique for the analysis of biogenic amines and phenols as their 1-dimethylaminonaphthalene-5-sulphonyl (dansyl) derivatives is described, particularly as regards to the linearity and sensitivity of detection. The mono derivatized amines gave a linear response over the range 10-9 to 10-14 mol, with a few being detected in quantities as small as 5 × 10-15 mol. The bisdansyl derivatives have a lower sensitivity and the response is linear over a more restricted range, terminating at 10-13 mol. Deuterated analogues of some of the amines were prepared and the feasibility of their use as internal standards was investigated. In this way, the problems associated with quantitative biochemical analyses caused by losses during extractions, chromatographic separations and thermal decomposition in the mass spectrometer lon source are overcome. The differentiation of isomers of biogenic amines as their dansyl derivatives has been accomplished by fractional sublimation and by examination of differences in their fragmentation patterns.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bms.1200010202
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