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Biomedical subjects

J Tedroff

Publications and source records attributed to J Tedroff.

43 records · Page 3Linked to original sources
PubMed1990

Pharmacokinetics and effects of levodopa in advanced Parkinson's disease.

Five patients with severe Parkinson's disease were characterized with respect to their pharmacokinetic and pharmacodynamic responses to levodopa given: orally, intravenously (three different infusion rates) and intraduodenally. The best therapeutic infusion rate in the intravenous study was used for the intraduodenal infusion of levodopa. A lag time between plasma concentration and effect following oral administration was seen in three of the five patients and this disequilibrium was estimated as the rate constant Ke0 using model-independent analysis. The plasma concentration-effect relationship was similar for the three modes of administration and in all patients the therapeutic plasma concentration for full mobility was greater than 4-5 micrograms.ml-1. The disequilibrium half-life for development of effect after oral administration was calculated to be about 30 min. The patients remained clinically stable during the period of the intraduodenal infusion.

Administration, Oral↗
PubMed1990

Striatal kinetics of [11C]-(+)-nomifensine and 6-[18F]fluoro-L-dopa in Parkinson's disease measured with positron emission tomography.

The kinetics in brain of the dopamine reuptake blocking agent [11C]-(+)-nomifensine and the L-dopa analogue 6-[18F]fluoro-L-dopa were compared in 3 patients with idiopathic Parkinson's disease and age-matched healthy volunteers using positron emission tomography. Regional uptake was analyzed and quantified according to a 3-compartment model. Retention of both tracers in striatal regions of the parkinsonian patients were reduced compared with the healthy volunteers mainly in the putamen, while the caudate nucleus was only mildly affected. The reductions were considerably less than the decrease previously reported postmortem for striatal dopamine content in the basal ganglia of patients with Parkinson's disease. A fairly constant ratio between 6-[18F]fluoro-L-dopa utilization and [11C]-(+)-nomifensine binding in the caudate nucleus and the putamen were found in both groups unrelated to the size of the estimated parameters. This indicates that a limiting factor for the utilization of exogenous levodopa in Parkinson's disease may be a reduced transport capacity for the amino acid into the dopaminergic terminals.

Adult↗
PubMed1989

Synthesis of racemic (+) and (-) N-[methyl-11C]nomifensine, a ligand for evaluation of monoamine re-uptake sites by use of positron emission tomography.

The synthesis of racemic or enantiomeric N-[methyl-11C]nomifensine (1,2,3,4-tetrahydro-2-[11C]methyl-4-phenyl-8-isoquinolinamine), a potential ligand for the evaluation of monoamine re-uptake sites at the presynaptic dopaminergic terminals, using the appropriate N-desmethylcompounds and [11C]methyl iodide is described. The radiochemical conversion of [11C]methyl iodide to [11C]nomifensine was in the order of 85-95%. Radiochemical purity of the LC-purified radiopharmaceutical was in the order of 98-99%. In a typical run, starting with 120 mCi (4.4 GBq) of [11C]carbon dioxide, 380 MBq (8.6% not decay corrected) of a final solution was obtained within 55 min (roughly 20 min of that is related to transport time). The specific radioactivity corresponding to the [11C]methyl iodide was 30-100 mCi/mumol (typical: a total mass of 30 micrograms and 150 MBq was administered in the PET-studies). A procedure for resolving the racemate of N-desmethylnomifensine (1,2,3,4-tetrahydro-4-phenyl-8-isoquinoline) into its enantiomers using triacetylcellulose as the stationary phase and methanol/ethanol as solvents by use of LC is also described.

Adult↗
PubMed1989

Brain dopaminergic mechanisms in Parkinson's disease evaluated by positron emission tomography.

The meso-striatal dopamine neurons, essential for the automated control of movements, are primarily affected in patients with P.D. Direct study of the role of this pathway in states of disease has not been possible until recently and the application of PET for the in vivo investigation of dopaminergic mechanisms may serve to demonstrate the potential of the technique. One basic idea has been to work out methods to investigate multiple aspects of dopaminergic function, i.e. presynaptic mechanisms such as re-uptake sites and synthesis of neurotransmitter as well as postsynaptic such as receptor properties. Furthermore, efforts have been made to evaluate dopamine degradating enzymes. Preclinical PET-investigations have regularly been performed in Rhesus monkeys and the hemiparkinsonian model produced by infusing MPTP into one internal carotid artery has been of great value to characterize new 11C-labelled tracers. Today 11C--(+)-nomifensine is used to give a measure of dopamine re-uptake sites, probably reflecting nerve terminals. 11C-labelled L-dopa has now been introduced and can be expected to replace 18F-L-fluorodopa as a physiological tracer for precursor transport and transmitter synthesis. Several ligands are available for the quantitation of dopamine receptors--11C-N-methylspiperone and 11C-raclopride have been used in our studies. 11C-L-selegiline and its "inactive" D-form have been used in clinical PET-studies aimed to evaluate the enzyme MAO-B. A summary of in vivo information of dopaminergic mechanisms in P.D. obtained using the above-mentioned tracers and PET is presented.

Brain↗
PubMed1988

Monoamine re-uptake sites in the human brain evaluated in vivo by means of 11C-nomifensine and positron emission tomography: the effects of age and Parkinson's disease.

Six patients with Parkinson's disease, selected to cover a range of clinical features, and 7 healthy volunteers aged 24-81 years, were examined by positron emission tomography after i.v. injection of racemic 11C-nomifensine, a catecholamine re-uptake blocking drug. After injection the radiotracer, radioactivity was rapidly distributed to the brain. The highest accumulation of radioactivity was found in areas rich in dopaminergic and noradrenergic innervation, such as the striatum and the thalamus. In regions with negligible dopaminergic and noradrenergic innervation, such as the cerebellum, radioactivity was lower and evenly distributed. In all investigated brain regions a marked age-related decline in 11C-nomifensine-derived radioactivity relative to the cerebellum was observed in the group of healthy volunteers. Parkinsonian patients did not show such a decline with age. In the group of parkinsonian patients with mainly unilateral involvement, the contralateral putamen exhibited the most pronounced decrease. Only the 3 parkinsonian patients aged 63 and younger showed markedly lower 11C-nomifensine binding in striatal areas than age-matched healthy volunteers. 11C-nomifensine seems to be a valuable tool for investigating noradrenergic and dopaminergic re-uptake sites in vivo. Further achievements will most likely be made when the active enantiomer becomes available.

Adult↗