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G Firnau

Publications and source records attributed to G Firnau.

46 records · Page 3Linked to original sources
PubMed1980

Blood-brain barrier transport and cerebral utilization of dopa in living monkeys.

[18F]fluoro-dopa, DL-3,4-dihydroxy-5-[18F]fluorophenylalanine, a tracer for dopa, was injected intravenously into cynomolgus monkeys anesthetized with enflurane, and the appearance of 18F in the head and the disappearance of 18F from the blood were each measured continuously for 10 min with simple gamma-ray detectors. A three-compartment explanatory model was used to derive fractional rate constants for the forward flux of L-dopa into the endothelium of the brain capillaries from the blood (1.54 +/- 0.37 min-1), the back flux of dopa and/or its metabolites to the blood from the endothelium (0.67 +/- 0.05 min-1), the formation of dopamine from dopa (0.20 +/- 0.04 min-1), and the destruction of dopamine (0.04 +/- 0.02 min-1). It was also shown that only one-fifth of the dopa that entered the endothelium was available for dopamine synthesis in neurons. It was concluded that the technique described could be extended to man and used to investigate the role of dopa and dopamine in the control of mood and locomotion.

Animals↗
PubMed1978

[18F]fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine.

3,4-Dihydroxy-5-fluorophenylalanine, fluorodopa, was injected into rats in which unilateral lesions of the nigrostriatal pathway had been made. The rats rotated towards the side with the lesions, thus providing further evidence that fluoro-dopa is an analogue of dopa. [(18)F]Fluoro-dopa was then injected intravenously into fully conscious baboons. A well-collimated scintillation detector, aligned along the occipitomental axis, recorded the accumulation of (18)F in the brain. Control animals accumulated (18)F continuously for 100 min. This accumulation represents net transport of [(18)F]fluoro-dopa from blood to brain, decarboxylation to [(18)F]fluoro-dopamine, storage, and degradation of [(18)F]fluoro-dopamine. alpha-Methyl-dopa, a competitive inhibitor of dopa transport and decarboxylation, prevented the accumulation of (18)F; reserpine, known to release stored intracerebral dopamine, discharged (18)F; pargyline, a monoamine oxidase inhibitor, and haloperidol, a known augmentor of intracerebral dopamine turnover, increased the rate of accumulation of (18)F. These changes in the accumulation of intracerebral (18)F, after [(18)F]fluoro-dopa, were commensurate with the known action of the drugs used to induce them and demonstrate the use of a gamma-emitting precursor of a neurotransmitter to monitor simply, atraumatically, and externally the intracerebral metabolism of the transmitter in fully conscious primates. When applied to man, the same technique should be able to provide more conclusive evidence than is presently available for the role of catecholamines in schizophrenia and depression. It should also provide further insight into the natural history of nigrostriatal diseases and the action of drugs used in their treatment.

Animals↗
PubMed1976

Why do Tc-99m chelates work for cholescintigraphy?

There are four structural requirements for substances that are excreted by the liver: 1. Their molecular weight is between 300 and 1,000. 2. They are organic anions. 3. They contain at least two ring systems in the molecule. 4. They are bound to serum albumin. All the Tc-99m chelates suggested for cholescintigraphy fulfill these requirements. For the first time a rational for their efficacy is provided.

Animals↗
PubMedDate not supplied

Dopamine visualized in the basal ganglia of living man.

The neurotransmitter dopamine has biological attributes that make it amenable to study by positron emission tomography, unlike many of the 40 or so neurotransmitters that have been identified in the brain. Dopamine deficiency in the nigrostriatal system is a characteristic of Parkinson's disease, and a disturbance of dopamine metabolism is still widely held to be responsible for the syndrome of schizophrenia. Despite its importance in the regulation of locomotion and mood, it has been impossible to visualize the intracerebral distribution of dopamine and measure its regional metabolism in man. In the first demonstration of the regional distribution of a neurotransmitter in the brain of conscious normal man, we show here that L-3,4-dihydroxyphenylalanine (L-dopa) labelled in the 6-position with the positron-emitting radionuclide fluorine-18, localizes specifically in the dopaminergic pathways of the human brain where its turnover could be measured atraumatically by positron emission tomography.

Adult↗