Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016053 (fibromyalgia)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pfizer is developing pregabalin, a follow-up compound to its GABA agonist gabapentin, for the potential treatment of several central nervous system (CNS) disorders including epilepsy, neuropathic pain, anxiety and social phobia [286425]. By December 2000, Pfizer anticipated filing an NDA for pregabalin for seven major indications (beginning with neuropathic pain and add-on epilepsy), with the FDA by the end of 2001. Filings for generalized anxiety disorder (GAD), social anxiety disorder and fibromyalgia are expected to take place in 2002, and filings for epilepsy monotherapy and panic disorders are expected to take place in early- and late-2003, respectively [336918], [393182], [399956]. By January 2001, pregabalin was in phase II development in Japan for the potential treatment of neuropathic pain, with an anticipated approval date of 2005 [394827]. However, following analysis by the FDA of a mouse study that showed incidence of a specific tumor type, Pfizer announced in February 2001, that it is restricting the use of pregablin in some clinical patients [398726] and it has frozen trials for neuropathic pain [398785]. In April 2001, Morgan Stanley Dean Witter predicted potential sales of $350 million in 2002, rising to $1750 million in 2006, with peak sales in excess of $2000 million [406923].
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PMID:Pregabalin (Pfizer). 1157 65

Some chronic diseases have a favourable course and are cured spontaneously. Allergic diseases such as eczema, hay fever and asthma have a good outcome in more than 75% of cases within 7 to 25 years, depending on the kind of allergy. Migraines have also a good evolution in children and after menopause. Many symptoms due to menstruation such as dysmenorrhea, premenstrual syndrome or anemia, disappear after menopause as well as diseases due to estrogens such as uterine leiomyoma, endometriosis and prolactinoma. The risk of epilepsy relapse after a first seizure is about 40% after 2 years. The risk is lower in children. Attention deficit disorder affects 3 to 5% of children but is present in only 30% of them in adult age. The prevalence of depression decreases in women between 30 and 60 years of age. Functional somatic syndromes such as fibromyalgia, irritable bowel syndrome or dyspepsia decrease in 2/3 of cases within 5 to 10 years if there is no history of anxio-depressive symptoms. However, prognosis is reserved when initial symptoms are severe or if they are connected to sexual abuse, domestic violence or depression. Other diseases have a spontaneous favourable course such as myopia, idiopathic infertility, polycystic ovary disease or ventricular arrhythmia. The knowledge of a good prognosis enables to avoid unnecessary treatments and to reassure many patients.
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PMID:[The benefits of aging. I. Patience and cure: spontaneous beneficial course of certain diseases]. 1172 11

The main mechanisms of the chronopathological forms of magnesium depletion associate a low Mg intake with various dysregulating biorhythms. The differentiation between forms with hyperfunction and forms with hypofunction of the biological clock is seminal and the main marker is the production of melatonin (MT). The clinical forms of the various patterns of the chronopathological forms of Mg depletion may be central or peripheral. The clinical forms with hyperfunction of the biological clock (marker: increase in MT) may associate diverse expressions of nervous hypoexcitability: depression (i.e. Seasonal affective disease); cephalalgias nocturnal, without photophobia (i.e. cluster headaches); dyssomnia LASPS (advanced sleep phase syndrome) particularly]; asthenia and myalgias (i.e. fibromyalgia, chronic fatigue syndrome). The main comorbidity is found with depressive states. The therapy relies on classical bright light phototherapy, sometimes associated with psychoanaleptics. The clinical forms with hypofunction of biological clock (marker: decrease in MT) may associate various signs of nervous hyperexcitability (HEN): anxiety (from generalized anxiety to panic attacks); cephalalgias diurnal with photophobia (mainly migraine); dyssomnia [DSPS (delayed sleep phase syndrome) particularly, jet lag, night work disorders, age related insomnia, sometimes with inappropriate behaviour; photogenic epilepsia, generalized or focal; some clinical forms of chronic fatigue syndrome and fibromyalgia. The main comorbidity is between migraine and epilepsia. The treatment relies on the diverse forms of darkness therapy, possibly with the help of some psycholeptics: anxiolytics and anticonvulsants. The indications of chromatotherapy remain to be validated.
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PMID:Chronopathological forms of magnesium depletion with hypofunction or with hyperfunction of the biological clock. 1263 82

Pregabalin is a gamma-aminobutyric acid analog that is under development by Pfizer for the potential treatment of central nervous system disorders, including epilepsy, neuropathic pain, fibromyalgia and generalized anxiety disorder. By April 2003, Pfizer had filed for approval of pregabalin in Europe for neuropathic pain and as an adjunctive therapy for epilepsy, and in October 2003 an NDA was filed for these indications and generalized anxiety disorder. At this time, phase III trials in fibromyalgia were ongoing.
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PMID:Pregabalin (Pfizer). 1498 79

Quality of life is an important indicator in assessing the burden of disease, especially for chronic conditions. The Health Utilities Index (HUI) is a recently developed system for measuring the overall health status and health-related quality of life (HRQL) of individuals, clinical groups, and general populations. Using the HUI (constructed based on eight attributes: vision, hearing, speech, mobility, dexterity, cognition, emotion, and pain/discomfort) to measure the HRQL for chronic disease patients and to detect possible associations between HUI system and various chronic conditions, this study provides information to improve the management of chronic diseases. This study is of interest to data analysts, policy makers, and public health practitioners involved in descriptive clinical studies, clinical trials, program evaluation, population health planning, and assessments. Based on the Canadian Community Health Survey (CCHS) for 2000-01, the HUI was used to measure the quality of life for individuals living with various chronic conditions (Alzheimer/other dementia, effects of stroke, urinary incontinence, arthritis/rheumatism, bowel disorder, cataracts, back problems, stomach/intestinal ulcers, emphysema/COPD, chronic bronchitis, epilepsy, heart disease, diabetes, migraine headaches, glaucoma, asthma, fibromyalgia, cancers, high blood pressure, multiple sclerosis, thyroid condition, and other remaining chronic diseases). Logistic Regression Model was employed to estimate the associations between the overall HUI scores and various chronic conditions. The HUI scores ranged from 0.00 (corresponding to a state close to death) to 1.00 (corresponding to perfect health); negative scores reflect health states considered worse than death. The mean HUI score by sex and age group indicated the typical quality of life for persons with various chronic conditions. Logistic Regression results showed a strong relationship between low HUI scores (< or = 0.5 and 0.06-1.0) and certain chronic conditions. Age- and sex-adjusted Odds Ratio (OR) and p values showed an effect among individuals diagnosed with each chronic disease on the overall HUI score. Results of this study showed that arthritis/rheumatism, heart disease, high blood pressure, cataracts, and diabetes had a severe impact on HRQL. Urinary incontinence, Alzheimer/other dementia, effects of stroke, cancers, thyroid condition, and back problems have a moderate impact. Food allergy, allergy other than food, asthma, migraine headaches, and other remaining chronic diseases have a relatively mild effect. It is concluded that major chronic diseases with significant health burden were associated with poor HRQL. The HUI scores facilitate the measurement and interpretation of results of health burden and the HRQL for individuals with chronic diseases and can be useful for development of strategies for the prevention and control of chronic diseases.
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PMID:Using Health Utility Index (HUI) for measuring the impact on health-related quality of Life (HRQL) among individuals with chronic diseases. 1534 14

Pregabalin (PGB) is a novel drug under development for the treatment of epilepsy, neuropathic pain, fibromyalgia, and generalized anxiety disorder. In this study, we investigated PGB transport in rats, mammalian cell lines, and Xenopus laevis oocytes. In contrast to gabapentin (GBP), PGB absorption in rats showed unique linear pharmacokinetics. PGB entered CHO and Caco-2 cells predominately via Na(+)-independent processes. Uptake of PGB was mutually exclusive with leucine, GBP and 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid, the substrates preferential for system L. The preloaded PGB in CHO cells was exchangeable with leucine, but at a lower exchange rate than that of leucine and GBP. Dixon plots showed competitive inhibition of leucine uptake by PGB, with a K(i) value very close to the K(m) value for PGB uptake (377 versus 363 microM). At an extracellular concentration of 300 microM, the intracellular PGB concentration in CHO cells reached 1.5- and 23-fold higher than that of GBP and leucine, respectively. In contrast, at clinically relevant concentrations, PGB seemed not to interact with GABA transport in GAT1, GAT2, and GAT3 cell lines, system y(+), b(0,+), B(0,+), and B(0) transport activities in Caco-2 and NBL-1 cells, and the b(0,+)-like transport activity in rBAT cRNA-injected X. laevis oocytes. Taken together, these results suggest that L-type transport is the major transport route for PGB and GBP uptake in mammalian cells. The differential affinity of PGB and GBP at L-type system leads to more concentrative accumulation of PGB than GBP, which may facilitate PGB transmembrane absorption in vivo.
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PMID:Mediation of highly concentrative uptake of pregabalin by L-type amino acid transport in Chinese hamster ovary and Caco-2 cells. 1576 62

The term 'Ca2+ channel alpha2delta ligands' has recently been applied to an evolving drug class that includes gabapentin (Neurontin) and pregabalin (Lyrica), and reflects significant progress over the past decade in elucidating the mechanism of action of these drugs: a novel, specific action at one of the subunits constituting voltage-sensitive Ca2+ channels. Binding of these ligands to the alpha2delta subunit is considered to explain their usefulness in treating several clinical disorders, including epilepsy, pain from diabetic neuropathy, postherpetic neuralgia and fibromyalgia, and generalized anxiety disorder. The evidence indicates a relationship between alpha2delta subunit binding and the modulation of processes that subserve neurotransmission. This modulation is characterized by a reduction of the excessive neurotransmitter release that is observed in certain neurological and psychiatric disorders.
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PMID:Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission. 1722 65

Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health, disease, and aging. A wide range of seemingly unrelated disorders, such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis, have underlying pathophysiological mechanisms in common, namely reactive oxygen species (ROS) production, the accumulation of mitochondrial DNA (mtDNA) damage, resulting in mitochondrial dysfunction. Antioxidant therapies hold promise for improving mitochondrial performance. Physicians seeking systematic treatments for their patients might consider testing urinary organic acids to determine how best to treat them. If in the next 50 years advances in mitochondrial treatments match the immense increase in knowledge about mitochondrial function that has occurred in the last 50 years, mitochondrial diseases and dysfunction will largely be a medical triumph.
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PMID:Mitochondrial dysfunction and molecular pathways of disease. 1723 70

Transcranial direct current stimulation (tDCS) and caloric vestibular stimulation (CVS) are safe methods for selectively modulating cortical excitability and activation, respectively, which have recently received increased interest regarding possible clinical applications. tDCS involves the application of low currents to the scalp via cathodal and anodal electrodes and has been shown to affect a range of motor, somatosensory, visual, affective and cognitive functions. Therapeutic effects have been demonstrated in clinical trials of tDCS for a variety of conditions including tinnitus, post-stroke motor deficits, fibromyalgia, depression, epilepsy and Parkinson's disease. Its effects can be modulated by combination with pharmacological treatment and it may influence the efficacy of other neurostimulatory techniques such as transcranial magnetic stimulation. CVS involves irrigating the auditory canal with cold water which induces a temperature gradient across the semicircular canals of the vestibular apparatus. This has been shown in functional brain-imaging studies to result in activation in several contralateral cortical and subcortical brain regions. CVS has also been shown to have effects on a wide range of visual and cognitive phenomena, as well as on post-stroke conditions, mania and chronic pain states. Both these techniques have been shown to modulate a range of brain functions, and display potential as clinical treatments. Importantly, they are both inexpensive relative to other brain stimulation techniques such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS).
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PMID:The use of tDCS and CVS as methods of non-invasive brain stimulation. 1790 Jul 3

Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health and disease. Damage to mitochondria is now understood to play a role in the pathogenesis of a wide range of seemingly unrelated disorders such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis. Medications have now emerged as a major cause of mitochondrial damage, which may explain many adverse effects. All classes of psychotropic drugs have been documented to damage mitochondria, as have stain medications, analgesics such as acetaminophen, and many others. While targeted nutrient therapies using antioxidants or their precursors (e. g., N-acetylcysteine) hold promise for improving mitochondrial function, there are large gaps in our knowledge. The most rational approach is to understand the mechanisms underlying mitochondrial damage for specific medications and attempt to counteract their deleterious effects with nutritional therapies. This article reviews our basic understanding of how mitochondria function and how medications damage mitochondria to create their occasionally fatal adverse effects.
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PMID:Medication-induced mitochondrial damage and disease. 1862 87


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