Peripheral Catecholamine Metabolism Research Articles

The effects of the COMT inhibitor entacapone on haemodynamics and peripheral catecholamine metabolism during exercise.

1. Catechol-O-methyltransferase (COMT) inhibition might be assumed to potentiate the effects of circulating catecholamines, particularly under conditions of enhanced catecholamine release. 2. The purpose of the present study was to establish whether the novel COMT inhibitor, entacapone, changes haemodynamic responses and catecholamine metabolism during exercise. 3. Entacapone was given orally to 12 healthy male subjects (age 23-30 years) in increasing single doses from 0 mg (control day) to 200 mg. A submaximal exercise test was performed on a bicycle ergometer, and blood pressure, heart rate and ECG were recorded. The concentrations of noradrenaline, adrenaline, DHPG (3,4-dihydroxyphenylglycol), MHPG (3-methoxy-4-hydroxyphenyl-glycol) and, DOPAC (3,4-dihydroxyphenylacetic acid) in plasma were determined. 4. Entacapone did not influence haemodynamics or ECG at rest or during exercise. 5. Entacapone did not influence plasma catecholamine levels, either at rest or during exercise. However, it altered the metabolic profile of catecholamines, which was shown by increases in the plasma concentrations of the monoamine oxidase-dependent metabolites DHPG (by up to 100%) and DOPAC (by up to 53%), and by a decrease of the COMT-dependent metabolite MHPG (by up to 29%).

Changes in peripheral metabolism of catecholamines in guinea-pig during thermal adaptation

1. 1.|Catecholamines and their final metabolites were determined quantitatively in urine of guinea-pigs ( Cavia aperea porcellus) during thermal adaptation by means of high performance liquid chromatography (HPLC) with electrochemical detection (ECD). 2. 2.|The daily release of free noradrenaline (NA) and 3-methoxy-4-hydroxyphenylglycole (MHPG) increased in cold adapted animals (5°C) up to 500% at the beginning of the third week of cold exposure (in comparison to animals kept at 22°C). Warm adapted animals (28°C) reduced NA and MHPG excretion by nearly 50%. 3. 3.|No significant changes in excreted amounts of adrenaline (A), dopamine (DA) and homovanillic acid (HVA) could be detected during thermal adaptation. 4. 4.|From these data it can be concluded that the exposure of warm adapted guinea-pigs to cold may lead to a 10 times higher peripheral release and turnover of NA.

Study on monoamine metabolite contents of cerebrospinal fluid in patients with neurodegenerative diseases.

Main monoamine metabolities of cerebrospinal fluid (CSF), i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), were measured in 74 patients with neurodegenerative diseases, in 30 normal control subjects and in 16 diseased control subjects without neurodegenerative diseases. The symptoms of patients were scored according to an original scale. It was suggested by statistical study including multiple regression analysis that there might be significant relationship between CSF-MHPG level and extrapyramidal symptoms, or autonomic symptoms, and between CSF-5-HIAA level and extrapyramidal, or cerebellar symptoms, and between CSF-HVA level and extrapyramidal, pyramidal, or cerebellar symptoms. It was also suggested that the severer the symptoms of patients with Parkinson's disease, Shy-Drager syndrome, or olivopontocerebellar atrophy became, the lower the levels of monoamine metabolities of CSF became. The activity of peripheral catecholamine metabolism might influence the CSF-MHPG level because of the significant positive correlations between CSF-MHPG level and urine noradrenaline or vanillylmandellic acid level. The level of MHPG was high in patients with severe amyotrophic lateral sclerosis or hereditary spinocerebellar degeneration possibly because of stress with respiratory dysfunction.

Neurochemical aspects in pathogenesis of alcohol and drug dependence

At present, catecholamines are considered to play a significant role in the regulation of psychic function and emotional states. Our investigations have revealed significant changes in peripheral catecholamine metabolism in alcoholic patients. Catecholamine metabolism in the brain and in the periphery are rather autonomous, and thus in our studies we compared the effects of alcohol on dopaminergic and noradrenergic systems in different brain regions as well as in the periphery. We found a significant decrease in noradrenaline levels in different regions of the CNS, particularly midbrain, hypothalamus and hippocampus. In chronic studies with rats, catecholamine metabolism was studied in animals chronically treated with alcohol, those treated with a single dose after chronic treatment, and those animals undergoing withdrawal from alcohol. Neuropharmacological and neurochemical studies were accompanied by electrophysiological monitoring of the effects of alcohol.