Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The frissonnant (fri) mutation is an autosomic recessive mutation which spontaneously appeared in the stock of C3H mice. fri mutant mice have locomotor instability and rapid tremor. Since tremor ceases when mutant mice have sleep or are anaesthetized, and because of their obvious stereotyped motor behavior, these mice could represent an inherited Parkinsonian syndrome. We show here that the fri/fri mouse fulfills two out of the three criteria required to validate an experimental model of human disease, that is isomorphism, homology and predictivity. Indeed, fri/fri mice present an important motor deficit accompanying visible tremor and stereotypies. They display some memory deficits as in human Parkinson's desease. l-Dopa and apomorphine (dopaminergic agonists), ropinirole (selective D2 agonist), and selegiline (an monoamino-oxidase B [MAO-B] inhibitor) improve their clinical status. However, neither anatomopathological evidence of nigrostriatal lesion, nor decrease in tyrosine hydroxylase production could be seen.
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PMID:The frissonnant mutant mouse, a model of dopamino-sensitive, inherited motor syndrome. 1144 53

Parkinson's disease (PD) is a common, debilitating, neurodegenerative disorder characterized by neuronal loss within the basal ganglia and insufficient levels of the neurotransmitter dopamine. Symptoms include resting tremor, rigidity, bradykinesia (slowness of voluntary movement), and postural disturbances. Exact cause is unknown, but theories surrounding environmental or endogenous toxicities have been suggested. Differential diagnoses include genetic and other neurologic disorders that may share symptoms similar to those seen in PD. Clinical progression has been categorized into three phases of the disease: early, nonfluctuating, and fluctuating. Medications generally offer good symptom relief during the early and nonfluctuating phases of the disease. Classifications of anti-PD medications include anticholinergics, dopamine agonists, amantadine, MAO-B inhibitors, levodopa-carbidopa, and Catechol-o-methyl transferase inhibitors. Surgical intervention may be an option for select patients whose conditions are not well controlled though medical management strategies. Primary care providers often can manage patients in the early stage of PD, but later stages require expert neurologic management. Patient/family education and anticipatory guidance is imperative.
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PMID:Understanding Parkinson's disease: detection and early disease management. 1193 73

Parkinsonism (PD) is a neurodegenerative disorder of the brain resulting in dopamine deficiency caused by the progressive death of dopaminergic neurons. PD is characterized by a combination of rigidity, poverty of movement, tremor and postural instability. Selegiline is a selective and irreversible propargylamine type B monoamine oxidase (MAO-B) inhibitor. This drug, which inhibits dopamine metabolism, has been effectively used in the treatment of PD. However, its therapeutic effects are compromised by its many neurotoxic metabolites. To circumvent this obstacle, a novel MAO-B inhibitor, rasagiline, was developed. Paradoxically, the neuroprotective mechanism of propargylamines in different neuronal models appears to be independent of MAO-B inhibition. Recent investigations into the neuroprotective mechanism of propargylamines indicate that glyceraldehyde-3-phosphate dehydrogenase (GAPDH), MAO-B and/or other unknown proteins may represent pivotal proteins in the survival of the injured neurons. Delineation of the mechanism(s) involved in the neuroprotective effects exerted by MAO-B inhibitors may provide the key to preventive novel therapeutic modalities.
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PMID:Neuroprotection by monoamine oxidase B inhibitors: a therapeutic strategy for Parkinson's disease? 1469 44

Recent clinical evidence indicates that the broad spectrum anticonvulsant drug lamotrigine is effective against the depressive phase of bipolar illness and the difficult to treat rapid cycling form of the disorder. However, the molecular mechanism underlying this therapeutic action remains uncertain. Given that inhibition of the A-type of monoamine oxidase (MAO) is a proven antidepressant mechanism, we investigated the effects of lamotrigine on MAO activities in vitro and on monoamine disposition in vivo. In vitro, lamotrigine inhibited rat brain MAO activities with Ki values (MAO-A, 15 microM; MAO-B, 18 microM) potentially within the therapeutic range for this drug. The effects of lamotrigine on the MAO-A activities of rat brain and human liver preparations were almost identical suggesting minimal species or tissue variation. In contrast, there was no (MAO-A) or minimal (MAO-B) reduction in brain MAO activities when assayed ex vivo following the administration of lamotrigine to rats. In vivo brain microdialysis failed to detect meaningful alterations in extracellular hippocampal or frontal cortex monoamine concentrations. Furthermore, lamotrigine did not modulate oral tyramine-induced hypertension in rats or 5-hydroxytryptophan-induced head shaking in mice, providing strong evidence that the drug does not perturb monoamine metabolism in vivo. The absence of observable effects of lamotrigine on monoamine disposition in vivo may be explained by the competitive and highly reversible nature of the interaction of lamotrigine with MAO isoforms. Thus, altered monoamine metabolism in vivo is unlikely to account for the antidepressant action of the drug in bipolar depression.
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PMID:Effect of lamotrigine on the activities of monoamine oxidases A and B in vitro and on monoamine disposition in vivo. 1612 25

Parkinson's disease (PD) is the most common cause of parkinsonism. Parkinsonism is characterized by resting tremor, bradykinesia, rigidity and gait impairment. There is no specific diagnostic test for PD and it is important for clinicians to understand the clinical signs which help to distinguish PD from parkinsonism. It is equally important to be aware of the clinical signs which can be an indication that the diagnosis is not PD. These so-called Parkinson-plus syndromes include progressive supranuclear palsy (PSP), multiple systems atrophy (MSA), corticobasal degeneration (CBD), vascular parkinsonism (VP) and parkinsonism with dementia (Lewy body dementia, LBD). The differential diagnosis of parkinsonism will be discussed. Initiating pharmacologic therapy for PD must take into consideration the degree of dysfunction the patient is experiencing, the question of neuroprotection, the degree of motor response required, and the potential complications of long-term treatment. Neuropro-tective trials of coenzyme Q10 (CoQ), vitamin C, vitamin E, monoamine oxidase B inhibitors (MAO-I) and dopamine agonists do not support the use of any of these drugs for a neuroprotective effect. There is recent supportive evidence that levodopa may have a neuroprotective effect. Either dopamine agonists or levodopa may be initiated. Dopamine agonists are associated with fewer motor fluctuations and dyskinesias, while levodopa is associated with better motor performance. Initiation of therapy should be tailored to individual patients with the emphasis on symptom control, with the hope that new approaches to treatment of PD (including neuroprotection) will be forthcoming.
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PMID:Parkinson's disease. Diagnosis and the initiation of therapy. 1617 58

5-hydroxytryptamine (5-HT) syndrome is a dangerous condition of 5-HT excess that can occur in the case of co-administration of a monoamine oxidase (MAO) inhibitor and a serotonin reuptake inhibitor (SSRI). The goal of the present study was to investigate the effects of acute administration of MAO inhibitors and subchronic administration of fluvoxamine on 5-HT-related behaviors (head shaking and 5-HT syndrome) in rats treated with 5-hydroxytryptophan (5-HTP). Administration of the non-selective MAO inhibitor, pargyline, and the selective MAO-A inhibitor, clorgyline, resulted in 5-HT syndrome in 5-HTP-treated rats, and subchronic co-administration of fluvoxamine intensified the syndrome. However, administration of the selective MAO-B inhibitor, selegiline, did not induce 5-HT syndrome with or without subchronic fluvoxamine co-administration. These data suggest that non-selective MAO and selective MAO-A inhibitors can induce 5-HT syndrome in humans when co-administered with SSRI. Further, the risk of 5-HT syndrome may be lower with the selective MAO-B inhibitor, selegiline.
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PMID:Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats. 1648 9

The development of treatment for the symptoms of Parkinson's disease (PD) has been one of the most notable successes of neurology. Dopaminergic therapies in the form of levodopa, dopamine agonists, or monoamine oxidase B inhibitors significantly improve the characteristic motor symptoms of bradykinesia and rigidity, with a beneficial effect upon tremor in a proportion of patients. Novel delivery of dopaminergic drugs whether in the form of once a day sustained release preparations or transdermal applications ensures that they remain at the forefront of PD treatment. The development of drugs to slow the progression of PD has attracted considerable attention and there appears to be some measure of success although additional studies need to be performed. A range of nondopaminergic drugs including alpha 2-adrenergic antagonists, serotoninergics, and adenosine A2a antagonists are in late-stage development for PD and offer benefit for motor symptoms and motor complications.
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PMID:Future directions in the treatment of Parkinson's disease. 1817 1

Zonisamide (ZNS), a sulfonamide antiepileptic drug, is indicated as an adjunct therapy for partial seizure disorders with and without secondary generalization. ZNS has a favorable pharmacokinetic profile because of its rapid absorption and high bioavailability. Its activity is related to the blockade of voltage gated sodium and calcium channels, modulation of central dopaminergic, GABAergic, and serotonergic functions, as well as inhibition of carbonic anhydrase and monoamine oxidase B. ZNS has potential efficacy for an array of neuropsychiatric disorders including migraine and other headache syndromes, neuropathic pain, Parkinson's disease, essential tremor, stroke, obesity, anxiety, bipolar and binge-eating disorders.
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PMID:Therapeutic role of zonisamide in neuropsychiatric disorders. 1878 51

Serotonin toxicity is an iatrogenic complication of serotonergic drug therapy. It is due to an overstimulation of central and peripheral serotonin receptors that lead to neuromuscular, mental and autonomic changes. Moclobemide is a reversible inhibitor of monoamine oxidase (MAO)-A, selegiline is an irreversible selective inhibitor of MAO-B, and paroxetine is a selective serotonin reuptake inhibitor. Combined use of these agents is known to cause serotonin toxicity. A 53-year-old woman had been treated with paroxetine and selegiline. After moclobemide was prescribed in place of paroxetine without a washout period, she quickly developed confusion, agitation, ataxia, diaphoresis, tremor, mydriasis, ocular clonus, hyperreflexia, tachycardia, moderately elevated blood pressure and high fever, symptoms that were consistent with serotonin toxicity. Discontinuation of the drugs, hydration and supportive care were followed by remarkable improvement of baseline status within 3 days. This case demonstrates that serotonin toxicity may occur even with small doses of paroxetine, selegiline and moclobemide in combination. Physicians managing patients with depression must be aware of the potential for serotonin toxicity and should be able to recognize and treat or, ideally, anticipate and avoid this pharmacodynamically-mediated interaction that may occur between prescribed drugs.
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PMID:Serotonin toxicity caused by moclobemide too soon after paroxetine-selegiline. 1968 3

Parkinson's disease (PD) is caused by progressive degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in the deficiency of DA in the striatum. Thus, symptoms are developed, such as akinesia, rigidity and tremor. The aetiology of neuronal death in PD still remains unclear. Several possible mechanisms of the degeneration of dopaminergic neurons are still elusive. Various mechanisms of neuronal degeneration in PD have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium cytotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental factors, toxic action of nitric oxide, and apoptosis. All these factors interact with each other, inducing a vicious cycle of toxicity causing neuronal dysfunction, atrophy and finally cell death. Considerable evidence suggests that free radicals and oxidative stress may play key roles in the pathogenesis of PD. However, currently, drug therapy cannot completely cure the disease. DA replacement therapy with levodopa (L-Dopa), although still being a gold standard for symptomatic treatment of PD, only alleviates the clinical symptoms. Furthermore, patients usually experience severe side effects several years after the L-Dopa treatment. Until now, no therapy is available to stop or at least slow down the neurodegeneration in patients. Therefore, efforts are made not only to improve the effect of L-Dopa treatment for PD, but also to investigate new drugs with both antiparkinsonian and neuroprotective effects. Here, the advantages and limitations of current and future therapies for PD were dicussed. Current therapies include dopaminergic therapy, DA agonists, MAO-B inhibitor, COMT inhibitors, anticholinergic drugs, surgical procedures such as pallidotomy and more specifically deep brain stimulation of the globus pallidus pars interna (GPi) or subthalamic nucleus (STN), and stem cell transplantation.
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PMID:Treatment strategies for Parkinson's disease. 2010 Dec 74


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