Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “COMT”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,675 records · Page 93Linked to original sources
PubMed2001

[Parkinson disease. Directed use of modern therapy].

The approval of new antiparkinsonian drugs such as novel dopamine agonists or COMT-inhibitors during the last years has improved the therapeutic possibilities in Parkinson's disease. The choice of the different drugs depends on their particular efficiency, their adverse effect profile, the stage of the disease, the cardinal symptoms, age, and comorbidity. Therefore the physician is challenged to adjust the therapeutic management of each patient to the particular medical and social needs. This article discusses the present therapeutic strategies for the different stages of the disease detailing the profile, the main applications and the most important side effects of each drug.

Antiparkinson Agents↗
PubMed2001

[Parkinson therapy 2001, especially apomorphine in idiopathic Parkinson syndrome].

Today (2001) most strategies for Parkinson's disease (PD) are symptomatic. The etiology of the disease is not known. There exists no possibility to inhibit the degeneration of dopaminergic neurons in the substantia nigra. There are hints (but no proofs) for neuroprotection. Beside levodopa a variety of alternative treatment options exists which enable a good and longer lasting control of symptoms (e.g. dopamine agonists, COMT-inhibitors etc.). Apomorphine can reduce off-periods and fluctuations remarkably, even in more advanced stages of PD. Some patients may take profit from neurosurgical procedures (especially deep brain stimulation of subthalamic nucleus and globus pallidus internus). Rehabilitative/supportive approaches complete the medical regime, but there is no proof of efficacy.

Antiparkinson Agents↗
PubMed1996

[The disgrace of Antoine Daquin, first physician of Louis XIV (1693)].

Antoine Daquin, Principal Physician of Louis XIV and Earl of Jouy-en-Josas, was born in Paris. He was the son of Louis-Henri Daquin, Physician to Queen Marie de Médicis; his paternal grandfather, born in the Jewish religion, became converted to catholicism at Aquino, in Italy, whence his name d'Aquin, then Daquin. A. Daquin studied to be a doctor at Montpellier and graduated on 18 May 1648. He married Marguerite Gayant, Antoine Vallot's niece, Antoine Vallot being the Principal Physician of Louis XIV. This relationship permitted him to get the position of Principal Physician of the Queen, then, after Vallot's death, to succeed him, on 18 April 1672, as Principal Physician of the King. The kindliness of the King's mistress, Mme de Montespan, helped him in that appointment. Daquin was a good doctor, he turned out awkward: "great courtier, but rich, miser, grasping, wanting to establish his family anyway" said the Duc de Saint-Simon. He dared ask the King for the Archbishopric of Tours for his son: "it was the rock on which he broke up" said again Saint-Simon. On 2 November 1693, the comte de Pontchartrain came to his home by order of the King, to tell him, he was ordered to retire from Court without delay. It was forbidden him to come back or to write to the King. Guy-Crescent Fagon was designated "Premier Médecin" instead of him; but Fagon had worked at the undoing of Daquin, with a view to robbing him of his position, with the complicity of the King's new mistress, Mme de Maintenon. After his disgrace, Daquin retired probably to Moulins; he died obscurely in Vichy, on 17 May 1696. Today, Daquin is regarded as a victim of intrigues of Court, which explains his celebrity.

Famous Persons↗
PubMed1994

[Anton Nyström: the first practitioner in dermatology in Sweden and the controversy about his book on skin disorders].

Anton Nyström (1842-1931), practitioner and author, was at the end of the nineteenth and the beginning of the twentieth century a well-known but also controversial personage in Swedish cultural and intellectual life. The posterity remembers him mainly for having introduced the philosophical system of Auguste Comte and founded a Society for Positivism in Sweden as well as having founded an institution ("Arbetarinstitutet") in Stockholm with the purpose to give an all-round education to the working classes through lectures by leading personalities in the world of culture and science. In numerous publications he treated besides medical topics also religious, cultural, social, political and historical themes. Immediately after his medical graduation in May 1868, he went abroad to study dermatology and stayed for this purpose for nearly one and a half years in Vienna, Paris and London. Back in Sweden in the autumn of 1869, he began writing a book with the title "Theoretical and practical essays on skin disorders." This book is for us today interesting because it illustrates the different views of that time on skin diseases held by Hebra in Vienna, Bazin and Hardy in Paris and Wilson and Tilbury Fox in London. In Paris Nyström had been fascinated by Bazin's and Hardy's theories on constitutional diseases and diathetic states and had, as he says, "embraced the doctrines of Bazin". In Vienna, however, he had disapproved of Hebra's way to reject speculations on internal etiology for skin diseases and to look upon them as having mainly an external cause and of his method to treat skin diseases preferably with local remedies. In London he was on very friendly terms with Tilbury Fox, who to his satisfaction also sympathized with the opinions held by Bazin. ...

Dermatology↗
PubMed1994

[Charcot's epistemological concept].

Through a brilliant medical way, Charcot was, at the same time, rheumatologist, geriatric, clinician, pathologist - and mainly neuro-pathologist - ending as a psychiatrist (according to todays medical terminology). Here, we will point out how much scientific theory and philosophy may support an original concept very unusual during the second half of XIXth century medicine. Describing connection between biology and medicine according to Auguste Comte thoughte, the author is thoroughly going into the course introduced by Charcot: scientific medicine instead of empirical one; structural medical-anatomy against rudimentary approach and rising of experimental medicine; impact of human sciences on medical knowledge; appearance of specialists near general practitioners; idea of organic disturbances denying any 'faith healing". In fact, Charcot asserts that bedside instruction prevails against accurate sciences.

Clinical Medicine↗
PubMedDate not supplied

[Catecholamine concentration and metabolism in old age].

As shown by examination in apparently healthy persons aged from 20 to 100 years and in experiments on 1--28-month-old albino rats there was a significant change with the progress of age in the content and ratio of catecholamines in the blood, various organs and the urine. The blood noradrenaline level fell considerably; Na/A coefficient also dropped sharply. Catecholamine content in the organs changed irregularly: in the kidneys it increased, in the skeletal muscles--remained unchanged, in the adrenal glands, the heart, the spleen and the liver--decreased. There was a significant reduction with the progress of age of the urinary excretion of adrenaline, noradrenaline, DOPA and vanilyl-amygdalic acid. Elemination of the intravenously injected noradrenaline from the blood of old rats was markedly delayed in comparison with that in the young animals. Depression of the COMT activity did not alter the noradrenaline level in the heart of adult and old rats. Administration of ipraside caused an increase in noradrenaline content in the heart of old rats, but failed to alter it in adult animals. It is suggested that in the catecholamine metabolism of old animals prevalence is given to the processes of oxidative desamination.

Adrenal Glands↗
PubMedDate not supplied

[Successful treatment of primary myelofibrosis with thrombocytosis during pregnancy with alfa-interferon].

Primary myelofibrosis is predominantly a disease of old age, poor prognosis and no curable treatment. Thrombocytosis was observed in only 12% of patients. To our knowledge, there is only one reported case of a young woman with primary myelofibrosis who had a term pregnancy [1]. We report on a 29-year-old woman with thrombocytosis and medical history of two miscarriages in the last 2 years, the iirst at 30 weeks of gestation and the second at 27 weeks. Multiple placental infarctions were observed. She was without symptoms but with moderate splenomegaly 4.5 cm below left costal margin). The platelet count was 651 x 10(9)/L, WBC 7.2 x 10(9)/L with normal differential formula, and haemoglobin level 12 g/dl. Bone marrow biopsy showed fibrotic phase of primary myelofibrosis, with hyperplasia of megacaryocytes, decreased numbers of erythroid and granulocytic cells, and increased amounts of reticulin fibres. Cyctogenetic examination of the bone marrow showed normal female caryotype. Increased numbers of progenitors CFU-Mk, CFU-GM and BFU-E were observed in peripheral blood, and decreased numbers in bone marrow cultures. As the patient wished to become pregnant, the treatment with interferon-a (Roferon A) was started at a dose of 3 MU s.c., three times per week. The platelet count rapidly decreased at a level of 260-370 x 10(9)/L. The pregnancy was diagnosed 5 months later. At the 24 week of pregnancy, platelet count raised to 690 x 10(9)/l and the dose of interferon-a was augmented, 3 MU every day, until delivery. Foetal growth and placental circulation were monitored by serial ultrasonography. At the end of 34 weeks of pregnancy, it was noted that placental flow became insufficient, and after foetal lung maturity was stimulated with dexamethasone, Cesarean section was performed. Male baby was born, weighting 2000 g, with respiratory distress syndrome. This complication was successfully treated, and the child is now one year old, with normal growth and development. The mother is still on therapy with interferon-a, 3 MU, three times a week, and the last blood count was as follows: haemoglobin 10.7 g/dl, WBC 6.1 x 10(9)/L and platelet comt 437 x 10(9)/L. In conclusion, according to the clinical results of interferon-d in thrombocytosis and experimental studies which showed the absence of placental transfer of interferon-d, this therapy could be recommended to women with primary myelofibrosis who wish to have a baby.

Adult↗
PubMedDate not supplied

[Camptocormia, a rare form of motor system disorders in Parkinson's disease].

Camptocormia is characterized by pronounced forward flexion of the thoracolumbar spine, which increases while walking and disappears in recumbent position. The clinical spectrum of the described disorders with concomitant camptocormia is heterogenous. It was described for the first time in idiopathic Parkinson's disease in 1999. The pathophysiology of this phenomenon remains unclear but seems to be not related to antiparkinsonian treatment. The authors present the case of a 54 years old woman, with idiopathic Parkinson disease diagnosed 5 years ago. The rapid progression of the disease was associated with good response to Levodopa therapy, although the dose had to be increased up to 1400 mg/d (with peripheral decarboxylase and COMT inhibitor). After 5 years she developed painful spasms of paraspinal muscles which resulted in trunk flexion. The clinical picture resembled the described cases of camptocormia. There was no correlation between the appearance of camptocormia and the regime of levodopa administration (time or dosage). Therefore, one can conclude, that presumably camptocormia is not a form of dystonia of the trunk but, the result of till now unclear other factors (dysfunction in other non-dopaminergic nigrostriatal projections?).

Antiparkinson Agents↗
PubMed2002

Effect of germ-line genetic variation on breast cancer survival in a population-based study.

Somatic genetic alterations in tumors are known to correlate with survival, but little is known about the prognostic significance of germ-line variation. We assessed the effect of germ-line variation on survival among women with breast cancer participating in a British population-based study. Up to 2430 cases for whom current vital status data were available were screened for BRCA1/2 mutations and genotyped for polymorphisms in 22 DNA repair, hormone metabolism, carcinogen metabolism, and other genes. The effect of genotype on outcome was assessed by Cox regression analysis. The largest effect was observed for the silent polymorphism D501D (t>c) in LIG4, a gene involved in DNA double-strand break repair. The estimated hazard ratio (HR) in cc homozygotes relative to tt homozygotes was 4.0 (95% confidence interval, 2.1-7.7; P = 0.002), and this effect remained after stratification by stage, grade, and tumor type [HR, 4.2 (1.8-9.4); P = 0.01]. Total length of a CYP19 IVS4 (ttta)(n) repeat was also associated with survival [HR, 0.9 (0.8-1.0); P = 0.01], but this became nonsignificant after stratification by stage, grade, and tumor type. Poorer survival was observed for 10 BRCA1 mutation carriers [HR, 4.1 (1.3-13); P = 0.047]; however, after adjustment for known prognostic factors, the HR estimate decreased to 2.0 and became nonsignificant (P = 0.4). CYP17 (P = 0.05) and TP53 (P = 0.06) polymorphisms showed marginally significant associations in unstratified analyses. No effect on survival was seen for polymorphisms in ATM, BRCA1/2, CHK2, KU70, NBS1, RAD51, RAD52, XRCC3, AR, COMT, NQO1, VDR, ADH3, CYP1A1, GSTP1, TGF-beta, or CDH1. Even if confirmed, the prognostic markers identified in this study are unlikely to replace current markers of prognosis such as estrogen receptor status. However, our results demonstrate the potential of the analysis of germ-line variation to provide insight into the biological determinants of response to treatment and prognosis in breast cancer.

Aged↗
PubMed2002

[Molecular genetics of mood disorders].

Mood disorders are common diseases and cause a big burden on society, including suicide. Because there are many treatment resistant cases in mood disorders, it is very important to elucidate the pathophysiology of this condition to establish its prevention and its treatment. Genetic epidemiological studies have shown that genetic factors have an important role in the pathophysiology of mood disorders; therefore the molecular genetics studies of this condition have been extensively performed, such as positional approach (i.e., linkage study) and candidate gene approach (i.e., association study). Linkage studies have shown some candidate locations that have been reproduced in two or more studies, such as 1q21-42, 4p16, 10q21-26, 11p15, 12q23-24, 13q11-32, 18p11, 18q21-22, 22q11-13, Xp11, and Xq24-28. Most association studies have until now focused on the neurotransmitter system as a candidate molecule including serotonin transporter, serotonin receptors, dopamine receptors, tyrosine hydroxylase, MAO-A, COMT, and tryptophan hydroxylase. Moreover, phamacogenetic studies also have been carried out in this field to develop new drugs as well as personalized medicine. Future molecular genetic studies will find out the mood-disorder susceptible genes and open the gate to true treatment and prevention of this disorder as the Human Genome Project attains its goal.

Drug Design↗
PubMed2002

[Nuclear medicine diagnosis of pheochromocytoma with metaiodobenzylguanidine].

Excess secretion of any of the adrenal cortical or medullary hormones contributes to a number of well-known clinical syndromes.. They may result from benign or malignant adrenal tumours, adrenal hyperplasia or, least frequently, from extra-adrenal disease. Differentiation among these possibilities is often impossible on clinical or biochemical grounds alone. Location of the site(s) of excess hormone production in the past depended on relatively insensitive or invasive radiological methods. The non-invasive evaluation began with X-ray computed tomography but the functional significance of anatomical abnormalities cannot be determined from CT scan. Incorporation of specific radiopharmaceuticals into the abnormal tissues allows scintigraphic localization of functional abnormalities with a high degree of efficacy. The combination of adrenal scintigraphy and kompjuterizovanom tomografijom CT or magnetskom rezonancijom MRI should in most cases obviatc the need for more invasive procedures. Phaeochromocytoma is rare in hypertensive population, affecting only an estimated of 0.1%. However, a high index of suspicion is essential, since these tumours have potentially life-threatening cardiovascular effects and their successful resection is curative. Important clinical clues include the presence of orthostatic hypotension in an untreated hypertensive, resistance of hypertension to standard therapy (including possible exacerbation by (beta-blockers). In most cases, the diagnosis can be established by demonstrating high levels of free catecholamines and their metabolites (metanephrines and Vanillylmandelic acid). Clonidine test may be important in some cases. The purpose of this study is to point that metaiodobenzylguanidine (mlBG) has proved to be a safe, sensitive and highly specific agent for the location of phaeochromocytoma. The first successful schinigraphic demonstration of phaeochromocytomas in man was reported in 1981, using a new radiopharmaceutical, 131l-metaiodobenzylguanidinc (mlBG). mlBG is an aralkyl-guanidine which structurally resembles noradrenaline sufficiently to be recognized and be stored in the catecholamine storage vesicles. Whereas unstored noradrenaline is rapidly degraded, the halogenated benzyl ring of mlBG conlers resistance to catechol-o-methyltransferase (COMT) while its guanidino side-chain is resistant to monoamine oxidase (MAO). Uptake of mIBG is inhibited by some inhibitors (reserpine, tricyclic antidepressants, cocaine, labetalol, calcium-chanel blockers...). 131I-mlBG is normally taken up by liver, spleen, myocardium and salivary glands. Thyroid uptake ol liberated radioiodide will also occur unless the thyroid is blocked with stable iodide. The normal adrenal glands are usually not seen but faint uptake may be visible 48-72 h after injection in up to 16% of cases. Hepatic uptake is maximal at 24 h, declining to very low levels by 72 h (even more rapid in patients with phaeochromocytoma. Dosimetric corlsiderations limit the amount of 131l-mlBG that is administered for diagnostic studies. This, coupled with the low detection efficiency of gamma cameras for the 364 keV photon of 131l, led to the introduction of 131l-mlBG as an adrenomedullary scintigraphic agent of choice. In our department we started with mIBG scintigraphy in 1985 and we treated near 1000 patients. In this study we are talking about 180 patients from the beginning of 1996 to the end of 2001 all treated with 131l-mlBG. Like the other worldwide experience with this agent our sensitivity was 88.58% and specificity of 98.46%. Positive predictive value was 88.5% and negative predictive value was 93.46%. False negative results were 6.52% and there were no false positive results. After all we can say that mlBG has proved to be a safe, sensitive and highly specific agent for the location of phaeochromocytoma and neuroblastoma. Other radiolabelled aralkylamines have been examined as potential adrenal medullary scintigraphic agents. None has demonstrated superiority over mlBG in animal or limited human studies. 131l-mlBG should always be considered the radiopharmaceutical of choice for imaging purposes if it is available. 131l-mlBG in high doses is successfully used in therapy of malignant phaeochromocytoma and especially in nuroblastoma.

3-Iodobenzylguanidine↗
PubMed2002

Role of adenosine in drug-induced catatonia in mice.

Parkinson's disease is one of the most common neurodegenerative disorders affecting large majority of population who are older than age of 65. Apart from dopamine, acetylcholine and glutamate, adenosinc has also been identified in the basal ganglia. Adenosine modulates the release of a variety of neurotransmitters including dopamine. In order to establish adenosine-dopamine interactions in drug-induced catatonia we studied the effect of adenosine in drug-induced catatonia in mice. In the present study adenosine dose dependently produced catatonia when assessed on rota-rod and bar tests in mice. Adenosine also potentiated the catatonic effect of perphenazine. L-dopa plus carbidopa or OR-486 (a potent centrally acting COMT inhibitor) completely reversed adenosine-induced catatonia. Since reversal by scopolamine of adenosine-induced catatonia was not to the same extent as with l-dopa and OR-486 it appears that catecholamines particularly dopamine rather than cholinergic modulation is more important in adenosine induced catatonia. The motor dysfunction (catatonia) could be easily assessed using rota-rod test apparatus in mice.

Adenosine↗
PubMed1976

Influence of thyroid hormone on norepinephrine metabolism in rat brain during maturation.

The effect of thyroid hormone on norepinephrine (NE) metabolism was investigated in various regions of the developing rat brain. Neonatal hypothyroidism, induced by daily propylthiouracil injection starting at birth, caused an increase in NE levels in the brain stem and hypothalamus. The turnover of brain NE, as indicated by its rate of depletion following alpha-methyl-p-tyrosine administration, was decreased in the hypothalamus of 30-day-old hypothyroid rats but was unchanged in the brain stem and basal ganglia. The activities of monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT) were decreased in certain brain regions of hypothyroid rats. The data suggest that thyroid hormone may influence the ontogenic patterns of NE metabolism in the brain.

Aging↗
PubMed2002

Genetics of suicidal behavior: candidate association genetic approach.

Suicidal behavior runs in families and seemed to be genetically determined in part and independent of the presence of psychiatric disorders. This review presents the current knowledge of candidate gene association studies in the field of suicidology. Concordance for monozygotic twins is about 13% Vs. 0.7% in dizygotics. It seems that there is a relationship to intermediate phenotypes such as impulsivity and aggression. The problem of studying complex traits and of ethnic stratification in heterogeneous population are major concerns in studying genetics of suicide. Family-based methods is one of the strategies to overcome stratification. We found a possible association of tryptophane hydroxylase gene polymorphism with depression and serotonin transporter promoter gene to violence traits by family-based methods. Recent data from the study of COMT. MAO and serotonin receptors genes polymorphisms are controversial at this stage. Future directions for research includes alternative phenotypes, endo-phenotypes and genome scan.

Adolescent↗
PubMed2002

Heritability, genetics and association findings in anorexia nervosa.

Anorexia nervosa (AN) is a severe psychiatric disorder, characterized by a combination of abnormal eating behavior and weight regulation with disturbances of attitudes toward body weight and shape. Prevalence is estimated at 1/1000, but with a high prevalence of the partial syndrome and a 10% mortality rate. This article reviews the findings concerning the heritability and the contributing genes of the disorder, with a focus on candidate genes. In family studies, a higher frequency of AN and BN was found among relatives of AN probands. The heritability rate was estimated at 0.71, similar to twin studies, which estimate 0.58-0.76. The search for genes responsible for the disorder focuses on the monoaminergic and peptidergic systems that are related to appetite and weight regulation. So far, for serotonin and dopamine there are no consistent findings in association studies of AN. However, in an Israeli study, an association was found between susceptibility for AN and the COMT gene, which is involved in monoamine metabolism. Another Israeli study found a relation between AN and the gene encoding for the potassium channel (hSKCa3), which is involved in regulation of neuronal activity. In the endocrine system an unequivocal finding was described of an association to the gene encoding the receptor for beta-estrogen. In the appetite and weight regulation system an association was described between AN and a marker of the uncoupling protein-2 and -3 chromosomal region, raising the likelihood that the mutation within the gene is close to a positive marker. To conclude, although there is a strong familial component in AN, so far the search for candidate genes has not been fruitful and further large scale prospective and adoption studies are needed to confirm genetic factors. We hope that relative studies using a wide genome scan, as well as subtyping the different types of AN, will bring us closer to understanding of the heritability of AN and enable the development of improved means of prevention and treatment.

Adolescent↗
PubMed1992

[Excretion of free catecholamines in urine and activity of some enzymes involved in catecholamine metabolism with arterial hypertension during menopause].

This study was performed in 60 women aged between 47-55 years (mean age 50.46 +/- 1.7), divided into two groups: premenopausal and postmenopausal. Each group was subdivided according to arterial pressure: with normal pressure and arterial hypertension. Daily urinary excretion of catecholamines was determined according to method of Euler and Lishajko, the activity of dopamine--beta-hydroxylase in serum according to Nagatsu et al. The activity of catechol-O-methyltransferase in erythrocytes according to Axelrod et al., the activity monoamineoxidase in serum according to Wurtman et al. Daily urinary excretion of vanilmandelic acid determined according to Pisano et al. It was found that women with menopausal arterial hypertension have significantly greater urinary excretion of adrenaline and noradrenaline (p < 0.001) in the premenopausal period, and adrenaline (p < 0.01) in the postmenopausal period. The activity of dopamine-beta-hydroxylase did not differ from the control group. The activity of COMT in erythrocytes of women and MAO in serum of women with menopausal arterial hypertension was significantly lower. Daily urinary excretion of vanillinmandelic acid in women with menopausal arterial hypertension was significantly lower.

Catechol O-Methyltransferase↗
PubMedDate not supplied

[The current therapies for parkinson's disease. Part I: pharmacological treatment].

The following article presents current views on the possibility of pharmacological treatment of Parkinson's disease (PD). Research conducted on drugs with potentially neuroprotective effects has changed the way we viewed the treatment of early stages of PD. Beginning treatment with the application of dopamine agonists decreases the risk of the occurrence of motor complications, particularly high with young individuals. The treatment of advanced stages of the disease currently requires the application of levodopa combined with other medicines, such as dopamine agonists or catechol-O-methyl transferase (COMT) inhibitors. Selecting treatment options should be individualized for each patient; it should take into account the variability of the clinical picture dependent on the progression of the disease, and the possibility of the occurrence of undesirable adverse effects of the drugs prescribed.

Antiparkinson Agents↗
PubMed1992

Plasma dopamine, urinary dopamine and their metabolites in chronic renal failure.

To assess the clinical features of the dopamine (DA) metabolism in chronic renal failure patients (CRF), measurements were made of the plasma DA, norepinephrine (NE), epinephrine (EN) and their urinary metabolites in 6 healthy controls and 13 CRF patients before and after administration of oral DA (KW-3160, Kyowa Hakko Kogyo Co., Ltd.). The data obtained, including that for impaired DA metabolites in the patients with chronic renal failure, can be summarized as follows: I) Synthesis: In the plasma, the DA, NE and EN levels were not significantly different in the CRF patients as compared to those in normal controls, but the excretions of urinary free DA, NE and EN were markedly lower, and the free and conjugated DA, NE and EN levels were significantly decreased in the CRF patients after DA administration. These findings indicate that the plasma dopamine beta-hydroxylase activity is inhibited in CRF patients. II) Degradation: Increased levels of urinary free and conjugated 3,4-dihydroxy phenylacetic acid (DOPAC) and decreased levels of urinary conjugated homovanillic acid (HVA) were observed, indicating that the monoamine oxidase (MAO) activity in the plasma is possibly augmented, and the catecholamine O-methyl transferase (COMT) activity inhibited, in uremic patients. III) Excretion: The urinary excretions of free DOPAC, HVA, NE and vanillylmandelic acid (VMA) and of conjugated DA and DOPAC were significantly correlated with the creatinine clearance. These data suggest that the excretion of urinary DA and part of its metabolites may be regulated by the renal function.

Administration, Oral↗