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  • 1
    ISSN: 1435-1463
    Keywords: Keywords: Salsolinol ; Parkinson's disease ; N-methylation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. An augmented synthesis of tetrahydroisoquinolines, such as salsolinol (SAL) or an increased N-methylation of these compounds has been addressed by various investigators as putative pathophysiologic mechanisms in Parkinson's disease (PD). Aim of this study was (1) to investigate putative relations between plasma levels of dopamine and R- and S-enantiomers of SAL and (2) whether these metabolic precursors of the neurotoxic N-methylated-SAL (NMSAL) are elevated in untreated "de-novo" Parkinsonian patients compared to age- and sex-matched healthy controls. Plasma levels of R- and S-SAL and dopamine did not significantly (R-SAL: p = 0.61, S-SAL: p = 0.51, dopamine: p = 0.84) differ in both groups. Parkinsonian patients' R-SAL plasma levels were inversely related to intensity (p = 0.03, r = −0.42) and duration of PD (p = 0.03, r = −0.43) in contrast to S-SAL and dopamine. Dopamine levels were not associated to R-SAL (p = 0.88, r2 = 0.0008) and S-SAL (p = 0.088, r2 = 0.12) neither in Parkinsonian patients nor in controls. We conclude, that an upregulation of N-methylation of tetrahydroisoquinolines takes place in PD by enzymes such as neutral N-methyltransferase specific for R-SAL. The activity of this enzyme has been found elevated in parkinsonian lymphocytes. This increased N-methylation by the N-methyltransferase specific for R-SAL leads to the known augmented levels of neurotoxic R-NMSAL in Parkinsonian patients compared to controls in the cenral nervous system especially in the beginning of PD.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Keywords: Dopamine receptors ; Growth Hormone ; alcoholism ; dopamine ; relapse ; neuroadaption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been hypothesized that dysfunction of dopaminergic neurotransmission is involved in the pathogenesis of alcohol addiction. Therefore, peripheral dopamine levels, sensitivity of central dopamine receptors (apomorphine-induced Growth Hormone (GH) secretion), and the inhibitory efficacy of G-proteins on adenylyl cyclase activity (as an indicator for dopamine D2-receptor coupled second messenger mechanisms) were measured in 45 alcohol-dependent patients before and after detoxification and in 10 healthy controls. The time needed to adjust to abstinence conditions differed between patients with good and poor treatment outcome. In subsequent abstainers, effects of alcohol withdrawal were already found during the first 24 hours of abstinence (normalisation of GH response, increases in dopamine levels and the inhibitory efficacy of G-proteins). During the next 7 days of abstinence, no more significant changes were observed in the assessed variables. In subsequent relapsers, no significant effect of acute ethanol withdrawal on the same measures was found. However, at day 8 of abstinence, increases in apomorphine-induced GH secretion (towards normalisation), in dopamine plasma levels, and in the inhibitory efficacy of G-proteins (towards above-normal levels) were observed. This retarded adjustment of dopaminergic signal transduction seems to reflect the relapse risk of treatment non-responders.
    Type of Medium: Electronic Resource
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