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PubMed1997

Involvement of Catecholestrogens in the release of pituitary hormones.

Catecholestrogens (CE), natural metabolic products of 17ß-estradiol and estrone, were assayed in anterior and posterior pituitary lobes and in the median eminence of the rat. The highest CE values were found in the median eminence and the lowest in the anterior pituitary. The CE concentrations in pars nervosa and pars intermedia of the posterior pituitary were quite similar. No sexual difference in the CE content was found in median eminence, anterior and posterior pituitary lobes. The highest CE concentrations were found in the median eminence and pars intermedia of lactating rats. During the estrous cycle median eminence CE showed maximal values in the morning of the proestrus, while anterior pituitary CE showed a decrease in the afternoon of the proestrus. Posterior pituitary lobe CE content did not change throughout the stages of the estrous cycle. Ovariectomy decreased CE content in the anterior pituitary but did not change the CE content in pars nervosa and pars intermedia of the posterior pituitary lobe. Estrogen therapy in ovariectomized animals increased CE content in pars nervosa. In the lactating rats, the separation of mothers from their pups for 4 h increased CE content in the posterior lobe and showed no variations in the anterior lobe. When pups were replaced and allowed to suckle for 5 and 30 min, CE content decreased in both the anterior and posterior pituitary lobes. Pars nervosa CE varied with suckling in the same way as the whole posterior lobe did. Pars intermedia and median eminence, both of which exhibited high CE values in the lactating rats, showed no CE variations in the model of separation/suckling. Parallel studies of COMT activity showed no variations in any model and in any pituitary lobe except anterior pituitary during the estrous cycle: COMT activity at Diestrus 2 was significantly low. The results obtained suggest that the CE are involved in the hormonal changes taking place in rat sexual cycle and lactation.

Journal Article↗
PubMed2000

[The new Parkinson's disease drugs].

The purpose of the new drugs for Parkinson's disease is control of the long-term levodopa treatment syndromes, especially wearing-off phenomenon and dyskinesia. Therefore, they show long T1/2. Most of them are classified into dopamine agonists. Others are monoamine oxidase B inhibitor and cathecole-o-methyltransferase inhibitor. Marketed dopamine agonists are bromocriptine, pergolide, talipexole, and cabergoline in Japan. Except talipexole, they are all ergot alkaloid derivatives. Their affinity for dopamine receptor is D2 group, and their T1/2 are longer than levodopa. Bromocriptine is an oldest dopamine agonist. Other 3 drugs and bromocriptine had made each other double blinded cross over trial previously. The result of double blinded studies show that their efficacy for PD treatment were equal, 40-50% patients with PD. However, in clinical usage, some difference is observed as described below. Efficacy of pergolide is strong compared with bromocriptine; however, pergolide is easy to arise dyskinesia. Talipexole is strong in the hypnosis effect. As for cabergoline, it takes long time to show medical effect, so that it is expected to control wearing-off phenomenon. Monoamine oxidase B inhibitor, Selegiline, is useful as an economizer effect to levodopa. As for the cathechole-o-methyltransferase inhibitor (COMT-I) will be make double-blinded trial in future. The efficacy for PD treatment of COMT-I is prolonged levodopa effect for PD, so that wearing-off phenomenon will be controlled. To use these drugs successfully is important with the treatment of PD. In the future, the development of the cause therapy in addition to the systematic therapy is wanted.

Antiparkinson Agents↗
PubMed1994

Tolcapone: a potential new antidepressant detected in a novel animal model of depression.

The potential antidepressant properties of tolcapone, a new catechol-O-methyl transferase (COMT) inhibitor, were investigated in a novel animal model of depression. Chronic mild stress (CMS)-induced anhedonia in rats is recognized as a model of depression with predictive and etiological validity. Here, the effects of CMS on the hedonic state of animals were assessed using a self-stimulation paradigm in which rats self-activate the ventral tegmental area. Frequency thresholds for self-stimulation responses were determined prior to, during and after a 19 day period of exposure to a variety of intermittent, unpredictable, mild stressors. In vehicle-treated stressed animals, stimulation threshold was significantly increased after about 12 days, reflecting a gradual development of an "anhedonic" state. This anhedonia persisted throughout the stress period and subsequently disappeared over a 10 day period. This stress-induced anhedonic state was not observed in stressed rats concomitantly treated with tolcapone (10 or 30mg/kg b.i.d.). In non-stressed vehicle- or drug-treated animals, no significant change in self-stimulation threshold was consistently observed. These results suggest that selective, reversible COMT inhibitors such as tolcapone may offer an innovative approach to the treatment of depression, in addition to their potential therapeutic use in Parkinson's disease.

Journal Article↗
PubMed2001

[Determination of catechol-O-methyltransferase activity in human erythrocytes by high performance liquid chromatography].

A rapid assay method for catechol-O-methyltransferase (COMT) activity in human erythrocyts by high performance liquid chromatography (HPLC) with UV detection was established. Enzyme activity was determined from erythrocyte lysates using S-adenosyl-L-methionine (SAM) as methyl donor and 3, 4-dihydroxybenzoic acid (DBA) as substrate. The 3-O-methylated reaction products were measured by HPLC with UV detection. The linear range of COMT was from 1 U/mL to 60 U/mL with an average RSD < 10%, and the detection limit was 0.5 U/mL(S/N > or = 5).

Adolescent↗
PubMed2003

[Associations between six functional genes and schizophrenia].

OBJECTIVE: To assess the associations between schizophrenia and six functional genes: dopamine D2 receptor gene (DRD2), dopamine D4 receptor gene (DRD4), 5-hydroxytryptamine 2A receptor gene (5-HT2A), 5-HT6 receptor gene (5-HT6), catechol-O-methyltransferase gene (COMT) and dopamine transporter gene (DAT1). METHODS: With the techniques of Amp-RFLP and Amp-FLP, association analysis was made between schizophrenia and the six genes in 67 schizophrenic patients from Chinese Han population. RESULTS: (1) Neither genotypes nor alleles of DRD2, 5-HT2A, 5-HT6 and COMT gene showed significant differences between patients and controls (P>0.05). (2) Six repeats (6R) in DRD4 gene, the allele of 480 bp and the genotype of 480/520 in DAT1 gene were found to be of significant differences between the two groups (P<0.05). (3) Only one negative association was observed between the 480 bp allele of DAT1 gene and schizophrenia (OR=0.441, 95% CI:0.202-0.963, Z=2.05, P<0.05). CONCLUSION: The 480 bp allele of DAT1 gene is negatively associated with schizophrenia in Chinese Han population, which stands for the dopamine hypothesis of schizophrenia.

Adult↗
PubMedDate not supplied

[6.7-Dihydroxycoumarin (Aesculetin) as a substrate for catechol-o-methyltransferase (author's transl)].

6,7-Dihydroxycoumarin (Aesculetin) was found to be a substrate of rat liver Catechol-O-methylfransferase (COMT) (EC 2.1.1.6). Incubation of this substrate with S-Adenosyl-L-[methyl-14C]methionine and/or S-Adenosylmethionin-hydrogensulfate in the presence of COMT yields the highly fluorescent compounds 7-hydroxy-6-methoxycoumarin (Scopoletin) and 6-hydroxy-7-methoxycoumarin (Isoscopoletin) in the ration of about 2:1. The O-methylated products obtained from Aesculetin were identified after separation by thin layer chromatography mainly by the reversed isotope dilution technique. The fluorescence of the isolated methylethers was proportional to concentration within the range from 10(-5)-10(-7) M. A reciprocal plot of activity versus substrate concentration gives a Km of 1 X 10(-6) M.

Animals↗
PubMed1992

The role of the regulatory enzymes of catecholamine synthesis in Parkinson's disease.

The major neuropathology of Parkinson's disease (PD) is the degeneration of nigrostriatal dopamine (DA), resulting in a deficiency of DA, and of the enzyme tyrosine hydroxylase (TH), which catalyzes the synthesis of L-dopa. The symptomatic treatment of PD consists of replenishing DA by administering L-dopa, which is enzymatically converted to DA in the striatum. The increase of TH activity by modification of the enzyme leads to an increased synthesis of striatal L-dopa, and thereby replenishes the missing DA more efficiently. The activity of TH is increased by protein kinase-dependent phosphorylation of the enzyme or by inhibition of dephosphorylation with specific phosphatase inhibitors. Thus, modification of TH results in an activated form of the enzyme, which might provide a basis for developing new strategies in the treatment of PD. The extraneuronal enzyme, catechol-O-methyl transferase (COMT), inactivates catecholamines by O-methylation, and its inhibition leads to increased levels of striatal DA. The availability of selective and nontoxic COMT inhibitors makes it possible to assess their therapeutic role in treatment of PD. The intraneuronal enzymes, monoamine oxidase (MAO)-A and MAO-B, inactivate catecholamines and other biogenic amines, such as serotonin, by deamination. Inhibition of these enzyme activities leads to increased levels of striatal DA. The irreversible MAO-B inhibitor selegiline was shown to exert antiparkinsonian activity, especially in the early stages of parkinsonism. Selegiline also prevents the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in MPTP-treated mice and monkeys. Its role in the prevention of the disease is under investigation in several clinical centers.

Catechol O-Methyltransferase↗
PubMed1992

Disposition of norepinephrine and epinephrine in jejunum of WLH chicken.

Disposition of (-)-norepinephrine and (-)-epinephrine in jejunum of WLH chicken was studied using oil-immersion technique. The relative rate of different routes of disposition of catecholamines was in the following order: for (-)-NE COMT greater than or equal to MAO greater than or equal to U2 greater than U1, for (-)-Epi U2 greater than or equal to COMT greater than MAO greater than U1. The role of enzymatic degradation is almost equal to that of uptake processes for (-)-Epi, but it was greater for (-)-NE.

Animals↗
PubMed2004

CNS dopamine oxidation and catechol-O-methyltransferase: importance in the etiology, pharmacotherapy, and dietary prevention of Parkinson's disease.

In this article, a particular emphasis has been placed on the conceptual development and understanding of the unique pathogenic changes that are indigenous to the striatal dopaminergic neurons as an important etiological factor in human Parkinson's disease (PD) as well as on the understanding of their clinical implications. Specifically, I have discussed the etiological roles of central nervous system dopamine oxidation in PD, along with a critical review of the available evidence in support of the proposed hypotheses. The chemically-reactive dopamine quinone/semiquinone intermediates are known to be highly neurotoxic and potentially genotoxic. There is considerable evidence for the suggestion that the long-term use of levodopa accelerates the progression of PD. In comparison, centrally-acting non-catechol dopamine receptor agonists would be an excellent alternative to levodopa for the treatment of PD (particularly for late-stage PD) because these agents would not undergo redox cycling to cause oxidative neuronal damage. Catechol-O-methyltransferase (COMT)-mediated methylation metabolism of catecholamine neurotransmitters is a crucial first-line detoxification pathway, and its role in the causation and prevention of PD is also discussed. On the basis of the modulation of COMT-mediated methylation of catecholamines, it is mechanistically explained that hyperhomocysteinemia would be a pathogenic factor in PD whereas vitamins B6, B12, and folate would be a protective factor. Lastly, according to the mechanistic understanding developed here, a novel dietary strategy is proposed that is specifically tailored toward lowering the risk of human PD, which includes eating a nutritionally-balanced diet that contains adequate (but not excessive) amounts of fruits and vegetables, along with adequate dietary supplementation of S-adenosyl-L-methionine, vitamins C, B6, B12, and folate. It is believed that these conceptual developments would also aid in our better understanding of other age-related neurodegenerative disorders, such as Alzheimer's and Huntington's diseases.

Animals↗
PubMed2004

[A comparative study of efficacy of dopamine receptors agonists and catechol-O-methyltransferase in the treatment of late stages of Parkinson's disease].

Dopamine receptors agonists and catechol-O-methyltransferase (COMT) inhibitors are the novel classes of the drugs for Parkinson's disease (PD) treatment in both early and late stages. In the latter one, there is an increase of substantia nigra neurons degeneration, striatum denervation, changes of dopamine receptors state, dysregulation of Levadopa uptake, dopamine synthesis and storage, decrease of dopamine receptors density in striatum that results in clinical picture alteration and development of pharmaco-therapeutic side-effects, as well as motor fluctuations and drug diskinesias. The use of dopamine receptors agonists and COMT inhibitors at the late PD stages in combination with other antiparkinsonian medications allows improving pharmaco-therapeutic efficacy, along with patient's daily activity and quality of life.

Activities of Daily Living↗
PubMed2005

Phytoestrogen exposure correlation with plasma estradiol in postmenopausal women in European Prospective Investigation of Cancer and Nutrition-Norfolk may involve diet-gene interactions.

Cross-sectional studies investigating the relationship between phytoestrogens in diet, urine, or blood with plasma estradiol and sex hormone binding globulin (SHBG) have been inconclusive. We investigated the relationship among phytoestrogen exposure, polymorphisms in the ESR1, COMT, CYP19, and SHBG genes, and plasma estradiol and SHBG levels in 125 free-living postmenopausal women taking part in a cohort study (European Prospective Investigation of Cancer and Nutrition-Norfolk) using three different markers: dietary, urinary, and serum phytoestrogens. Phytoestrogen levels (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) in spot urine and serum were analyzed by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry, respectively. Plasma estradiol and SHBG were measured by immunoassays. Adjusting for age and body mass index, urinary daidzein, genistein, glycitein, and serum daidzein and glycitein were negatively correlated with plasma estradiol (R = -0.199 to -0.277, P <0.03), with particularly strong associations found in the 18 women with CC genotype for ESR1 PvuII polymorphism (R = -0.597 to -0.834, P < 0.03). The negative correlations observed between isoflavones and estradiol in women as a whole became no longer significant when we excluded women with ESR1 PvuII CC genotype, indicating that the correlations observed were due mainly to this group of women. There was no relationship between dietary isoflavones and plasma estradiol and no association was found between any of the dietary, urinary, and serum phytoestrogen and plasma SHBG or between these factors and polymorphisms in CYP19, SHBG, and COMT. We conclude that higher isoflavone exposure is associated with lower plasma estradiol in postmenopausal women and that this preliminary study is suggestive of the involvement of diet-gene interactions.

Aged↗
PubMed2005

[A study of some genes related to serotoninergic and dopaminergic systems and auditory evoked-potentials (P300) in patients with schizophrenia and spectrum disorders and their first-degree relatives].

The changes of P300 parameters (lower amplitude and increased latency) are thought to be the most prominent phenomena of schizophrenia. A role of gene polymorphism in P300 generation was supported by several associative studies in psychiatrically well subjects and patients with mental disorders. We studied P300 parameters and the following polymorphisms: T102C for the serotonin receptor type 2A (5-HTR2A) gene, the 5-HTTLPR for the serotonin transporter gene, -809G/A, -616G/C N -52C/T SNPs in the promoter region of the dopamine D4 receptor (DRD4) gene and the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) in 74 patients with schizophrenia and spectrum disorders and 71 their first-degree relatives. No association was found between serotonergic system genes and P300. The -809G/A DRD4 gene polymorphism was related to amplitude in all frontal leads (p=0,01) in patients. In relatives, an association was observed between -521C/T DRD4 variants and latency (p=0,005) as well as between the COMT gene polymorphism and P300 amplitude (p=0,004) at the central lead. Thus, the genes involved in dopaminergic system play a role in P300 generation both in patients with schizophrenia and spectrum disorders and their relatives.

Adolescent↗
PubMed2006

Tolcapone: new drug. In Parkinson's disease: unacceptable risk of severe hepatitis.

(1) When patients with Parkinson's disease who are taking levodopa develop motor fluctuations that do not respond to dose adjustments, the standard treatment is the addition of bromocriptine, a dopaminergic agonist. Evaluation of entacapone fails to show whether the risk-benefit balance of this catechol-O-methyltransferase (COMT) inhibitor is at least as favourable as that of bromocriptine. (2) Tolcapone, another COMT inhibitor, is back on the French market after being withdrawn because of serious hepatic effects. The summary of product characteristics (SPC) specifies that tolcapone must only be used when entacapone treatment fails or is poorly tolerated. (3) Renewal of marketing authorisation was based on one clinical trial in which about half the patients were probably not resistant to entacapone. No difference in efficacy was found between tolcapone and entacapone. There is no firm evidence that tolcapone is effective in a significant number of patients in whom entacapone fails. (4) Placebo-controlled trials show that first-line treatment with tolcapone 100 mg to 200 mg 3 times a day reduces the duration of motor freezing ("off") periods, but the global impact of tolcapone on parkinsonism appears to be limited. (5) Unblinded randomised controlled trials have failed to show that tolcapone is more effective than bromocriptine or pergolide. There are no trials assessing the use of tolcapone in combination with dopamine agonists. (6) Adverse effects were frequent during clinical trials. They were mainly neurological and gastrointestinal, and differed from those associated with bromocriptine. In 1988, shortly after worldwide marketing of tolcapone, 3 cases of fatal fulminant hepatitis were reported among about 60 000 patients who had taken this drug. Some countries, including European Union member states, withdrew marketing authorisation. Other countries, including the United States, left tolcapone on the market but required stringent monitoring of liver function. Due to a lack of transparency on the part of both the manufacturer and the health authorities, we do not know if these measures reduced the risk of severe hepatitis. In the trial versus entacapone, one of the 75 patients treated with tolcapone 300 mg/day had an abnormal increase in serum transaminase activity. (7) In practice, tolcapone has a negative risk-benefit balance.

Antiparkinson Agents↗
PubMed1975

Supersensitivity to catecholamines after impairment of extraneuronal uptake or catechol-O-methyl transferase.

In cat papillary muscle and nictitating membrane block of extraneuronal catechol-O-methyl transferase (COMT) by 3',4'-dihydroxy-alpha-methyl propiophenone (U-0521) or of extraneuronal uptake by hydrocortisone causes supersensitivity to catecholamines whenever the experimental conditions result in a high sensitivity of the organ to catecholamines. After block of monoamine oxidase the extraneuronal O-methylation of (-)-[3H]norepinephrine by the isolated nictiating membrane is due to two O-methylating systems (Km and Vmax: 7.5 muM and 0.73 nmoles - g-1 - min-1, and 131 muM and 8.5 nmoles - g-1 - min-1, respectively). Hydrocortisone (28 muM) blocked the activity of the high affinity system without affecting the low affinity system. Apparently, there exists an extraneuronal compartment of high affinity that has a hydrocortisone-sensitive uptake mechnism; this compartment influences the concentration of catecholamines below the Km of this compartment. Supersensitivity ensues when either uptake or enzyme is blocked. Since the sensitivity effects of U-0521 and hydrocortisone are not additive, the high affinity compartment must a) metabolize most of the catecholamine transported into the compartment, and b) have a limited storage capacity for catecholamines after block of COMT.

Animals↗
PubMedDate not supplied

[Dopamine system genes and personality traits of extraversion and novelty seeking].

Dopamine neurotransmissin is thought to play a relevant role in behavioral reinforcement system. Polymorphism of the genes involved in dopamine system has been reported for association with psychological traits related to impulsive and sensation seeking behaviors. The study was aimed at a search for association of catechol-O-metyltransferase (COMT) and dopamine receptor D4 (DRD4) gene polymorphism with personality traits in Russian population. A sample comprised 130 subjects. It was found that carriers of the Met/Met COMT genotype had higher scores of novelty seeking as compared to those with the Val/Val and Met/Met genotypes. The association was observed in women only. In the presence of the C allele of the DRD4 gene, females with the Met/Met genotype demonstrated higher scores on extraversion and hypomania. The results are consistent with the current theoretical concepts on the regulation of dopamine neurotransmission in the brain.

Behavior↗
PubMed1990

[Methoxyflurane and ethanol do not inhibit the neuronal uptake of noradrenaline (uptake 1) at the desipramine binding site].

We recently demonstrated that the net accumulation of 3H-norepinephrine in the rat pheochromocytoma cell line PC12 was reduced by anesthetic concentrations of n-alkanols and the volatile anesthetics halothane, enflurane, isoflurane, and methoxyflurane. In PC12 cells, as in adrenergic neurons, norepinephrine is transported across the plasma membrane by a saturable, high-affinity, carrier-mediated mechanism (uptake1), which follows Michaelis-Menten kinetics, is energy- and sodium-dependent, and is inhibited by low concentrations of cocaine and the tricyclic antidepressant desipramine. Although uptake1 is the most important process for the removal of norepinephrine from the synaptic cleft, the net accumulation of norepinephrine within the neuron also depends on other factors including its vesicular uptake and storage within the granules, its metabolism by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT), and the efflux of its more lipophilic metabolites. In our previous report we could not exclude the contribution of any of these factors to the observed inhibitory effects of volatile substances. Therefore, the aim of the present study with ethanol and methoxyflurane was: (1) to elucidate further the exact mechanism responsible for the reduction of the norepinephrine accumulation; and (2) to investigate the anesthetics' interaction with the substrate recognition site, which is identical with the desipramine binding site on the norepinephrine carrier. METHODS. For 3H-norepinephrine uptake experiments, PC12 cells were cultured on dishes (60 mm, Nunc) coated with polyornithine. Reserpine (10 microM) was added to the culture 24 h before the experiment to deplete endogenous norepinephrine. The initial carrier-mediated transport rate (60 s) was measured as previously described. 3H-desipramine equilibrium binding was determined with isolated plasma membranes prepared from PC12 cells grown in suspension culture. The carrier-mediated uptake of 3H-norepinephrine and the specific 3H-desipramine binding were defined as those inhibited by 1 microM nisoxetine. All buffers contained 10 microM pargyline and 10 microM U-0521 to inhibit MAO and COMT. Incubations were done in the presence and absence of methoxyflurane (1% and 2% vol/vol in synthetic air containing 5% CO2) or ethanol (5% vol/vol). Media had been equilibrated with methoxyflurane by bubbling (30 min) and were routinely checked by gas chromatography. RESULTS AND DISCUSSION. Methoxyflurane and ethanol inhibited uptake1. However, reduction of uptake1 was far less pronounced than that previously found for the net accumulation of norepinephrine. Even at a vaporous concentration of 2% (corresponding with an over 15-fold half-maximal inhibitory concentration for norepinephrine accumulation), methoxyflurane produced only 58% inhibition of the high-affinity uptake...

Adrenal Gland Neoplasms↗
PubMedDate not supplied

[Metabolism of beta-adrenergic substances. Therapeutic implications].

The metabolism of the main beta-adrenoceptor stimulants which are not catechol derivatives involves conjugation with glucuronic or sulphuric acids in several animal species and conjugation with sulphuric acid in man. These drugs are not metabolized by MAO like isoproterenol or by COMT like the catechol derivatives: isoproterenol, trimetoquinol, hexoprenaline and rimiterol. Sulphate conjugation, in man, increases with the number of hydroxy groups. For salbutamol, pirbuterol, terbutaline and fenoterol, about 30%, 30%, 15% and 10% are respectively present in plasma as the unchanged active compound. Clenbuterol, a new specific beta 2-adrenoceptor stimulant, is a 4-amino-3,5 dichloro-benzene derivative and cannot be conjugated. It is cleared from the body mainly by the renal route (43% of the administered dose) and has eight minor metabolites, identical in several animal species and in man. Tulobuterol with no hydroxy substitute does not undergo conjugation, but is metabolized to 4-hydroxy tulobuterol. This metabolite is shown to be eight times more potent than tulobuterol. Metabolism depends greatly upon the route of administration: intravenous, subcutaneous, oral, by aerosol or instillation into the bronchial tree. Conjugation or COMT inactivation can take place in the gut wall (terbutaline), in lungs (isoproterenol, terbutaline, rimiterol) or by hepatic first-pass. These processes decrease the amount of drug reaching the blood and the receptor sites. Metabolism in the lung is important for ibuterol (terbutaline diisobutyrate), which is more lipophilic than terbutaline and spreads throughout tissues where it is hydrolyzed to active terbutaline. Biotransformations are determined by environmental or genetic factors and by the associated therapy and can change dramatically from one patient to another (interindividual variability) or for the same patient by multiple dosing (intra-individual variability). These differences in the rates of the metabolism can explain, partly, the differences observed in the response to beta-adrenoceptor stimulants by responder or non-responder patients. Decision about a therapeutic dosage regiment involves the choice of the drug, of the route of administration and of the dose. This choice is made on the basis of the dose/response relationship. In the kinetic approach, pharmacokinetic data obtained after a single dose facilitate the development of an appropriate dosage regimen.

Adrenergic beta-Agonists↗
PubMedDate not supplied

[Relationship between blood catecholaminergic variables in depressive patients and normal subjects].

Some biochemical assays are available to test the central NA activity in depressed patients. In several laboratories, two metabolites of NA, namely DHPG and MHPG, in either free, conjugated or total form, have been assayed indifferently for this purpose. The present report shows positive correlations between the level of the two glycols, as well as between their different forms in the plasma. In contrast, the level of erythrocyte COMT activity was not correlated with plasma MHPG, and did not show any change during the treatment with respect to the control pretreatment period in depressed patients. The values of MHPG showed a bimodal distribution in the patients before treatment; the plasma level of this metabolite decreased significantly in the first month of treatment, but did not change subsequently. The COMT activity values, as well as MHPG, were significantly correlated between the different time points, that is the control period and after 1 to 3 months of treatment.

Adult↗