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 1,711 records · Page 95Linked to original sources
PubMed2006

Long-term care of Parkinson's disease. Strategies for managing "wearing off" symptom re-emergence and dyskinesias.

Long-term care of elderly patients with Parkinson's disease (PD) is challenging for long-term care staff and physicians. Because the progression of PD varies among patients, an individualized treatment plan, updated as necessary based on disease progression, comorbid conditions, and side effects, is essential. Education regarding PD management is also needed to provide optimal care, and treatment guidelines from professional associations are available. Especially important is the management of motor complications, which usually emerge after treatment with antiparkinsonian medications, particularly levodopa/carbidopa. Current treatment strategies to avoid or treat motor complications aim at providing a more continuous (ie, physiologic) dopaminergic stimulation, rather than the pulsatile (intermittent) stimulation provided by traditional PD treatments. Catechol O-methyltransferase (COMT) inhibitors prolong the levodopa serum half-life and allow more levodopa to be delivered to the brain over a longer time, thereby smoothing dopaminergic stimulation. Dopamine agonists also provide more continuous dopaminergic stimulation but are associated with a greater likelihood of hallucinations and confusion, especially in the elderly. Treatments that reduce motor complications, allowing a higher level of functioning, lessen the burden of care in long-term care settings and increase quality of life for patients and their families.

Antiparkinson Agents↗
PubMed2006

Genetic risk for atherothrombotic cerebral infarction in individuals stratified by sex or conventional risk factors for atherosclerosis.

The aim of the present study was to assess the genetic risk for atherothrombotic cerebral infarction (ACI) in men and women separately as well as in individuals with or without conventional risk factors for atherosclerosis and thereby to contribute to the personalized prevention of ACI. The study population comprised 2705 unrelated Japanese individuals (1244 men, 1461 women), including 636 subjects (372 men, 264 women) with ACI. Subjects with ACI and controls either had or did not have conventional risk factors for atherosclerosis, including hypertension, hypercholesterolemia, and diabetes mellitus. The genotypes for 202 polymorphisms of 152 candidate genes were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis and a stepwise forward selection procedure revealed that 11 different polymorphisms were significantly (P < 0.005) associated with ACI in women or men or in individuals with or without hyper-tension, hypercholesterolemia, or diabetes mellitus: the 584C-->T polymorphism of LIPG, 5665G-->T of EDN1, and G-->A of CCL11 in women; 677C-->T of MTHFR, 1323C-->T of ITGB2, 3932T-->C of APOE, and -231A-->G of EDNRA in men; -572 G -->C of IL6 in hypertensive individuals; -403G-->A of CCL5 and G-->A of COMT in individuals with hypercholesterolemia; and 3932T--> C of APOE and A-->G of TNFSF4 in diabetic individuals. Polymorphisms associated with ACI may thus differ between women and men as well as among individuals with different risk factors. Stratification of subjects on the basis of sex or conventional risk factors for atherosclerosis may therefore be important in order to achieve the personalized prevention of ACI with the use of genetic information.

Aged↗
PubMed2006

Etiology and neurobiology of social anxiety disorder.

Social anxiety disorder (SAD) is influenced by multiple genetic and environmental factors. Imaging genomics combines genotyping with neuroradiological techniques, such as functional MRI (fMRI) and positron emission tomography (PET), to investigate samples relevant to psychiatric pathophysiology. Neuroanatomical areas implicated in SAD include the amygdala, prefrontal cortex, hippocampus, and striatum. Recent investigations have suggested that allelic polymorphisms may play a role in the disorder; 2 candidate genes, the serotonin transporter (SLC6A4) and catechol-O-methyl transferase (COMT), are described. The biology of extinction learning is relevant to therapeutic approaches that aim to augment existing psychotherapies. In the future, novel uses of imaging genomics integrated with rational, biologically informed treatments will offer a more refined understanding of this complex and disabling disorder.

Brain↗
PubMed1991

[Altruism and the donor].

On December 20, 1988, the government of France passed a law to protect people who voluntarily participate in biomedical research. This article makes extensive reference to a major study, titled From Biology to Ethics, by Jean Bernard, a well-respected authority in the field of bioethics. The author looks at models proposed by Bernard, as examples for health volunteers, in particular, the blood donor and the self-experimenter. To set the tone of the article, she recalls the concept of altruism, as first proposed by Auguste Comte, then makes a linkage between his philosophy and Bernard's point of view. By trial and error, in their discussions, various ethics committees and the French State Council have agreed upon what constitutes fair compensation under the law. Unlike their Canadian counterparts, medical researchers in France have free access to volunteers who are not in perfect health--e.g., the elderly, people suffering from kidney deficiency, cirrhosis of the liver, etc.--but these "experimental subjects" receive no monetary compensation. Thus, healthy and less-than-healthy volunteers do not receive equal treatment under the law. This inequity, added to the fear of what amounts to a tax on the human body and the difficulty of ensuring just compensation, is giving rise to a great deal of uncertainty.

Altruism↗
PubMedDate not supplied

Carrier-mediated outward transport of noradrenaline from adrenergic varicosities.

Normally, the carrier of the neuronal noradrenaline uptake mechanism (uptake1) is involved nearly exclusively in the inward transport of substrates. However, an outward transport is induced by either of two mechanisms: a. by the decrease (or reversal) of the Na+ concentration gradient across the neuronal membrane or b. by the "facilitated exchange diffusion" due to the inward transport of substrates of this carrier. In rat vasa deferentia (preloaded with 3H-noradrenaline; vesicular uptake, MAO and COMT blocked) all substrates of the carrier induced an outward transport of 3H-noradrenaline, in strict correlation with their Km for uptake1. The inward transport of these substrates increases the availability of the carrier on the inside of the neuronal membrane. However, additional factors contribute to this release: inhibition of re-uptake and co-transport of Na+ and Cl-. When vesicular uptake and MAO are intact, the strict correlation between Km and releasing effect was not seen. This is attributable to the very low axoplasmic concentration of 3H-noradrenaline under these conditions (i.e. to lack of substrate for outward transport). However, if substrates of uptake1 are also substrates of vesicular uptake, they are able to "mobilize" vesicularly stored 3H-noradrenaline and, hence, to induce substantial outward transport. These "good" releasers are identical with the "indirectly acting sympathomimetic amines" (i.e. they are tyramine-like).

Animals↗
PubMed1975

Pharmacological characteristics of the responses of rabbit oviduct to transmural stimulation.

The nature of the response of oestrogen dominant rabbit oviduct to transmural stimulation has been investigated. Both ampulla and isthmus responded to transmural stimulation with a single maintained response. This response was abolished by phentolamine, guanethidine, tetradotoxin and 6-hydroxydopamine showing that it resulted from the release of noradrenaline from adrenergic nerves and an action on alpha receptors. Propranolol had no effect on the responses of circular isthmic muscle suggesting that the beta receptors were relatively unimportant in determining the magnitude of the response. Cocaine failed to potentiate the magnitude of the response to field stimulation but did prolong the duration of the response. UO521, an inhibitor of COMT, had no effect on the responses of circular isthmus to transmural.

Animals↗
PubMed1989

Computerized rotometer apparatus for recording circling behavior.

A computerized rotometer for recording rotational behavior in rats is described. The digital pulses derived from the infrared photocell detector induced by animal rotations were input directly to a 20-megabyte microcomputer for on-line recording and were processed further to the Digital Equipment Corporation's VAX computer with the SAS software system for statistical and graphical analysis. The typical results obtained with drugs (apomorphine and amphetamine) eliciting contralateral and ipsilateral rotation in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the nigrostriatal dopamine pathway were presented. The effect of catechol-O-methyltransferase (COMT) inhibitor, OR-611, on the potentiation of L-dopa-induced contralateral rotation in 6-OHDA-lesioned rats was also studied. The automation of rotometer apparatus and the speed of data analysis facilitate screening novel antiparkinsonian drugs in rats with unilateral lesions of 6-OHDA.

Animals↗
PubMedDate not supplied

[Effect of corticosteroids on the action of sympathomimetics].

Corticosteroids restore the bronchial responsiveness to beta-adrenergic stimulants in man. This has been shown both in severe asthmatic patients and in normal subjects, rendered insensitive by artificial means. On the contrary, in patients with bronchial asthma who have airways reactive to beta-adrenergic stimulants, the combination of corticosteroids and sympathicomimetics results in an additive effect of their bronchodilating capacity. Animal models, both in vivo and in vitro, show the same type of interaction between corticosteroids and beta-adrenergic stimulants. The mechanism by which corticosteroids restore the bronchial sensitivity to beta-adrenergic stimulation is not completely understood. Several mechanisms may be involved such as increased agonist binding, decreased receptor turn-over, increased uncoupling between receptor and adenylcyclase, decreased extraneuronal uptake, decreased COMT-activity. The relevance of the influence of corticosteroids on the metabolism of membrane phospholipids remains highly speculative.

Adrenal Cortex Hormones↗
PubMed1987

An unusually important role of O-methylation in the disposition of noradrenaline and adrenaline by the dog renal artery.

Using the oil immersion technique, the role of neuronal uptake, monoamine oxidase and COMT in the inactivation of 2 concentrations (0.23 and 2.3 mumol/l) of noradrenaline and adrenaline was determined by the prolongation of the inactivation time caused by cocaine (12 mumol/l), pargyline (1 mmol/l) and U-0521 (50 mumol/l), respectively. The results obtained allow us to conclude that: 1) as previously shown, for the saphenous vein and mesenteric artery, noradrenaline is inactivated more rapidly than adrenaline; 2) in all tissues and for both concentrations of noradrenaline and adrenaline, neuronal uptake is more important for the inactivation of noradrenaline than for that of adrenaline, while O-methylation is more important for the inactivation of adrenaline than for that of noradrenaline. The only exception is that in the renal artery, O-methylation is very clearly the most important pathway of inactivation for both concentrations of both amines.

Animals↗
PubMed1986

[Biochemical factors of resistance to antidepressants].

This review of the literature concerning the biochemical factors of resistance to antidepressants is essentially based on the anomalies of neurotransmitters and the enzymes which regulate them. In the case of 5HIAA, because of the bimodal distribution in depressed patients, it appears to be generally accepted that when a low level of this catabolite is found in the cerebrospinal fluid, this may represent a factor of resistance to noradrenergic antidepressants, or even to all antidepressants. In contrast, a high level of this catabolite represents a factor of poor response to serotoninergic antidepressants. Low levels of urinary MHPG predict a poor response to serotoninergic antidepressants, while high levels are observed in cases of depression resistant to noradrenergic antidepressants. MAO activity, evaluated after two weeks' treatment with MAOI, is considered to be a biochemical factor of resistance when it is inhibited by less than 80%. High levels of COMT (related to the degree of anxiety and agitation) reflect a poor response to noradrenergic antidepressants. Finally, a number of strategies designed to control resistant depression (reserpine, lithium carbonate, ...) could, in certain cases, suggest the existence of a functional defect in the serotoninergic systems.

Antidepressive Agents↗
PubMed2026

Unraveling the Mystery of Pain: A Unique Clinical Encounter and Case Report.

BACKGROUND: The Clinical Pharmacogenetics Implementation Consortium published an updated guideline for opioids and CYP2D6, OPRM1, and COMT in December 2020. These guidelines include recommendations to avoid key opioids in patients who are ultrarapid or poor metabolizers of CYP2D6 to avoid toxicity and optimize efficacy. CASE REPORT: An older woman encountered a letter to the editor in a family magazine regarding genomically based responses to opioids. She reached out for more information and assistance, attesting to continued lack of analgesia to opioids prescribed during occasions of severe pain over the course of many years. A pharmacogenomic analysis proved to be the key to solving her mystery. CONCLUSION: Pharmacogenomic results may provide life-altering information transforming a patient's perspective on health care. Personalized medicine may be a key component in providing objective evidence for opioid treatment efficacy. There is a critical need for both provider and patient education to increase awareness of pharmacogenomics and how it can be applied to effective pharmacotherapy. Research is needed to explore appropriate, effective educational methods.

Humans↗
PubMed1979

[Influence of desoxycorticosterone on the reaction of isolated segments of coronary arteries to noradrenaline in the presence of pyrogallol].

The effect of the desoxycorticosterone on the noradrenaline-induced relaxation of coronary arteries waw studied in vitro, after a known inhibitor of COMT, pyrogallol. Relaxation induced by noradrenaline was enhanced by desoxycorticosterone. Relaxation in response to noradrenaline was increased by desoxycorticosterone. Pyrogallol potentiated the responses of coronary strips to noradrenaline and also reduced or abolished the enhancing effects of desoxycorticosterone. It is concluded that desoxycorticosterone enhances the reponse of coronary smooth muscle to noradrenaline by inhibiting and enzymatic pathway for the inactivation of catecolamines.

Animals↗
PubMed1978

[Influence of pyridoxal-5'-phosphate on the responses of isolated coronary arteries to adrenaline, in the presense of pyrogallol].

The effect of PLP on the adrenaline-induced relaxation of coronary arteries was studied in vitro, after known inhibitor of COMT, Pyrogallol. Relaxation of response to adrenaline were increased by PLP. Pyrogallol potentiated responses of coronary strips to adrenaline and also reduced or abolished the enhancing effects of PLP. It is concluded that PLP enhances the response of coronary smooth muscle to adrenaline by inhibiting a enzymatic pathway for the inactivation of catecholamines.

Animals↗
PubMed1978

[Influence of pyridoxal-5'-phosphate on responses of isolated coronary arteries to noradrenaline, in the presence of pyrogallol].

The effect of PLP on the noradrenaline-induced relaxation of coronary arteries was studied in vitro, after known inhibitor of COMT, Pyrogallol. Relaxation of response to noradrenaline were increased by PLP. Pyrogallol potentiated responses of coronary strips to noradrenaline and also reduced or abolished the enhancing effects of PLP. It is concluded that PLP enhances the response of coronary smooth muscle to noradrenaline by inhibiting a enzymatic pathway for the inactivation of catecolamines.

Animals↗
PubMed1984

Influence of supidimide on brain neurotransmitter systems of rats and mice.

The influence of 2-(2-oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1, 1-dioxide (supidimide), a representative of a new class of sedative drugs, on the noradrenergic, dopaminergic, serotoninergic and gamma-aminobutyric acid (GABA)ergic neuronal systems of rodent brains was investigated. In each case the brain transmitter levels after administration of supidimide were determined. Utilisation of noradrenaline (norepinephrine, NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) was also investigated ex vivo. The study was complemented with in vitro investigations of biosynthesis, synaptosomal uptake, degradation, and receptor binding of the transmitters. Based on a preliminary study of the distribution of [35S]-supidimide in rat brain, in vitro effects observed at greater than 10(-4) mol/l were considered irrelevant. Similarly, in vivo effects requiring dosages higher than 300 mg/kg i.p. were not regarded adequate to explain the sedative and antiaggressive efficacy of supidimide. With the above restrictions, the following parameters can be rated as not influenced by supidimide: levels of tryptophan in rat brain and serum (free and total); 5-HT biosynthesis in vivo (rat brain; 5-HT accumulation after monoamine oxidase (MAO) blockade); activity of MAO-A and MAO-B (rat brain mitochondria); uptake of 5-HT, NE and DA (rat synaptosomes); 5-HT receptor binding ( [3H]-LSD binding assay in rat cortical membranes); tyrosine hydroxylase activity (rat adrenal glands); catechol-O-methyl transferase (COMT) (rat liver); NE binding to central alpha 1- and alpha 2-receptors (rat brain; radioligand assay with [3H]-dihydroergocryptine, [3H]-prazosin and [3H]-WB 4101 (2',6'-dimethoxy-(G-3H]-phenoxy]-ethylaminomethylbenzo-1,4-dioxane ); DA levels (whole rat brain and striata); dihydroxyphenylacetic acid (DOPAC) levels (whole rat brain without cerebellum and striata); elevated DOPAC levels after pretreatment with haloperidol; DA-dependent adenylate cyclase in vitro (rat striatum); D2 receptor binding ( [3H]-spiperone binding assay, rat striatum); GABA levels (mouse brain); GABA transaminase activity (mouse brain stem); sodium-independent [3H]-GABA receptor binding (rat brain) and benzodiazepine binding (rat cortical membranes, [3H]-diazepam binding assay). Two effects on the GABAergic system were induced by supidimide. Starting at 300 mg/kg i.p., supidimide slowed down the GABA accumulation in brains of aminooxyacetate-treated mice. At 10(-4) mol/l supidimide caused a significant inhibition of GABA uptake (rat synaptosomes).(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dihydroxyphenylacetic Acid↗