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  • 1
    Electronic Resource
    Electronic Resource
    Central action of benserazide after COMT inhibition demonstrated in vivo by PET (1991)
    Springer
    Journal of neural transmission 85 (1991), S. 11-17 
    Details
    ISSN: 1435-1463
    Keywords: Tomography ; monkey ; L-DOPA ; aromatic L-amino acid decarboxylase ; catechol-O-methyltransferase ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Positron emission tomography (PET) following intravenous administration of β-[11 C]-L-DOPA provides a method of assessing regional cerebral uptake and utilization of levodopa. Cerebral levodopa kinetics in the rhesus monkey were investigated after the inhibition of catechol-O-methyltransferase (COMT) with RO 40-7592, and after coadministration of the peripheral aromatic L-amino acid decarboxylase (AADC) inhibitors benserazide and carbidopa. Pretreatment with RO 40-7592 (10 mg/kg), benserazide (10 mg/kg) or carbidopa (3.5 mg/kg) did not change striatal k3, which mainly reflects the ability for the brain tissue to convert [11C]-L-DOPA to [11C]-dopamine, although the brain's uptake of radioactivity increased substantially after pretreatment with the AADC inhibitors. When benserazide was coadministered with RO 40-7592 (10 mg/kg) a dose-dependent decrease in striatal k3 was measured with an apparent ED50 of 3 mg/kg. No such effect was indicated after pretreatment with the combination of RO 40-7592 (10 mg/kg) and carbidopa (3.5 mg/kg). The possible negative interactions of coadministration with COMT inhibitors and predominantly peripherally acting AADC inhibitors must be considered when used in the therapy of Parkinson's disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01244653
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  • 2
    Electronic Resource
    Electronic Resource
    Regional brain kinetics of 6-fluoro-(β-11C)-L-dopa and (β-11C)-L-dopa following COMT inhibition. A study in vivo using positron emission tomography (1992)
    Springer
    Journal of neural transmission 87 (1992), S. 15-22 
    Details
    ISSN: 1435-1463
    Keywords: (β-11C)-L-dopa ; 6-fluoro-(β-11C)-L-dopa ; positron emission tomography ; catechol-O-methyl transferase ; monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The regional brain kinetics of (β-11C)-L-dopa and 6-fluoro-(β-11C)-L-dopa was measured in six Rhesus monkeys using positron emission tomography (PET). Radioactivity accumulated specifically in the striatal region and the increase in L-dopa-derived radioactivity utilization with time was calculated using surrounding brain as a reference area, this being devoid of dopaminergic activity. The rate constant for selective striatal utilization i.e. grossly decarboxylation was 0.0110 ± 0.0007 (S.D) and 0.0057 ± 0.0006 min1 for (β-11C)-L-dopa and 6-fluoro-(β-11C)-L-dopa, respectively. After pre-treatment of the monkeys with the peripherally and centrally active catecholamine-O-methyl transferase (COMT) inhibitor Ro 40-7592 10 mg/kg, the decarboxylation rate remained unchanged (0.0112 ± 0.0015 min-1) for (β11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(β-11C)L-dopa (0.0092 ± 0.0015 min−1). Differences in the distribution of radiolabelled metabolites i.e. the corresponding O-methyl-L-dopa in the reference area is most probably the reason for the difference in calculated decarboxylation rate seen between the radiotracers. The higher decarboxylation rate measured for 6-fluoro-(β-11C)-L-dopa after blockade of COMT shows that the radiolabelled metabolites i.e. 6-fluoro-O-methyl-(β-11C)-L-dopa significantly contributes to background radioactivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01253107
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  • 3
    Electronic Resource
    Electronic Resource
    Pyridoxine effect on synthesis rate of serotonin in the monkey brain measured with positron emission tomography (1995)
    Springer
    Journal of neural transmission 102 (1995), S. 91-97 
    Details
    ISSN: 1435-1463
    Keywords: Serotonin ; 11C ; in vivo synthesis ; pyridoxine ; Rhesus monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of the co-factor pyridoxine, vitamin B6, on the activity of aromatic amino acid decarboxylase enzyme was studied by positron emission tomography, PET in the brain of the Rhesus monkey using the precursor for serotonin synthesis 5-hydroxy-L-tryptophan (5-HTP) radiola-belled with11C in the β-position. The rate constant for the formation of serotonin in the corpus striatum was calculated using a two tissue compartment model with reference area in the brain. In baseline investigations, the mean rate constants (±S.D:) for selective utilization of [11C]5-HTP to form [11C]serotonin in the corpus striatum was 0.0080 ± 0.0011 min−1. Pretreatment with intravenous pyridoxine hydrochloride 10 mg/kg bodyweight before doing a second PET study resulted in an enhanced rate constant by a mean of 20%. The rate increase was statistically significant. The increase varied considerably in different monkeys from no effect to more than 60%. The effect of pyridoxine on aromatic amino acid decarboxylase activity supported a regulatory role of pyridoxine on the synthesis of neurotransmitter in vivo, and may be of importance in diseases with deficiencies in neurotransmitter function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01276505
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  • 4
    Electronic Resource
    Electronic Resource
    Amphetamine effects on dopamine release and synthesis rate studied in the Rhesus monkey brain by positron emission tomography (1997)
    Springer
    Journal of neural transmission 104 (1997), S. 329-339 
    Details
    ISSN: 1435-1463
    Keywords: Amphetamine ; [11C] ; L-DOPA ; raclopride ; N-methylspiperone ; CBF ; PET ; monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Positron emission tomography (PET) was used in a multitracer protocol to evaluate D-amphetamine induced effects on dopamine biosynthesis rate and release in propofol anesthetized Rhesus monkeys.l-[β-11C]DOPA was used as biochemical probe to study the brain dopamine biosynthesis rate whilst dopamine release was followed by the binding displacement of the [11C]-radiolabelled dopamine receptor antagonists, raclopride and N-methylspiperone. Studies were performed with either a constant rate intravenous infusion of D-amphetamine aiming at plasma concentrations of 0.2 to 25 ng/ml or with intravenous bolus doses of 0.1 and 0.4 mg/ kg. Decreased binding of the dopamine receptor antagonists was measured in both modes of D-amphetamine administration but notably [11C]N-methylspiperone was less able to sense D-amphetamine induced release of dopamine. At plasma concentrations aimed above 1 ng/ml a levelling off of the binding of [11C]raclopride at 68 ± 8.1% of the baseline value indicated that displacement was only possible from a fraction of the binding sites. Amphetamine was observed to increase the rate constant forl-[β-11C]DOPA utilization in the brain. This was most likely due to an acutely induced subsensitivity of presynaptic dopamine receptors.l-[β-11C]DOPA and [11C]raclopride were found suitable to indicate changes in dopamine synthesis rate and release respectively using PET and can be used to mirror drug-induced changes of brain dopaminergic function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01277655
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  • 5
    Electronic Resource
    Electronic Resource
    Positron emission tomographic studies on aromatic L-amino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain (1993)
    Springer
    Journal of neural transmission 94 (1993), S. 127-135 
    Details
    ISSN: 1435-1463
    Keywords: 5-Hydroxy-L-(β-11 C)tryptophan ; L-(β-11 C)DOPA ; positron emission tomography ; aromatic amino acid decarboxylase ; monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The regional brain kinetics following 5-hydroxy-L-(β-11 C)tryptophan and L-(β-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or L-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 ± 0.0007 (S. D) and 0.0121±0.0010min−1 for 5-hydroxy-L-(β-11C)tryptophan and L-(β-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-(β-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4mg/kg of unlabelled compound. A decreased utilization rate of L-(β-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01245006
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