Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is still not established whether or not glucocorticoids are effective in the treatment of vestibular disorders such as dizziness and imbalance, although these drugs in combination with several others are used to treat dizziness and imbalance in some diseases. This study was undertaken to investigate the effects of a glucocorticoid, dexamethasone, on vestibular disorder following unilateral labyrinthectomy in pigmented rabbits. Neuronal activities of the medial vestibular nucleus (MVN) in alpha-chloralose-anesthetized cats were also investigated. Systemic injection of dexamethasone decreased the frequency of nystagmus and head deviation dose-dependently following hemilabyrinthectomy, and the rate of decrease was faster than that obtained by saline. In contrast, RU38486 (a glucocorticoid receptor antagonist) delayed the reduction of nystagmus and head deviation. Micro-iontophoretic application of dexamethasone rapidly enhanced the spontaneous firing of MVN neurons in a dose-dependent manner. These increases were blocked by RU38486, but not by GDEE (a glutamate receptor antagonist) or Co2+ (a Ca2+ channel blocker). These results suggest that dexamethasone directly activates the MVN neurons, thereby accelerating vestibular compensation.
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PMID:Role of glucocorticoid in vestibular compensation in relation to activation of vestibular nucleus neurons. 761 Aug 57

Retigabine [D23129; N-(2-amino-4-(4-fluorobenzylamino)-phenyl)carbamic acid ethyl ester] is an antiepileptic drug with a recently described novel mechanism of action that involves opening of neuronal K(V)7.2-7.5 (formerly KCNQ2-5) voltage-activated K(+) channels. These channels (primarily K(V)7.2/7.3) enable generation of the M-current, a subthreshold K(+) current that serves to stabilize the membrane potential and control neuronal excitability. In this regard, retigabine has been shown to have a broad-spectrum of activity in animal models of electrically-induced (amygdala-kindling, maximal electroshock) and chemically-induced (pentylenetetrazole, picrotoxin, NMDA) epileptic seizures. These encouraging results suggest that retigabine may also prove useful in the treatment of other diseases associated with neuronal hyperexcitability. Neuropathic pain conditions are characterized by pathological changes in sensory pathways, which favor action potential generation and enhanced pain transmission. Although sometimes difficult to treat with conventional analgesics, antiepileptics can relieve some symptoms of neuropathic pain. A number of recent studies have reported that retigabine can relieve pain-like behaviors (hyperalgesia and allodynia) in animal models of neuropathic pain. Neuronal activation within several key structures within the CNS can also be observed in various animal models of anxiety. Moreover, amygdala-kindled rats, which have a lowered threshold for neuronal activation, also display enhanced anxiety-like responses. Retigabine dose-dependently reduces unconditioned anxiety-like behaviors when assessed in the mouse marble burying test and zero maze. Early clinical studies have indicated that retigabine is rapidly absorbed and distributed, and is resistant to first pass metabolism. Tolerability is good in humans when titrated up to its therapeutic dose range (600-1200 mg/day). No tolerance, dependence or withdrawal potential has been reported, although adverse effects can include mild dizziness, headache, nausea and somnolence. Thus, retigabine may prove to be useful in the treatment of a diverse range of disease states in which neuronal hyperexcitability is a common underlying factor.
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PMID:Retigabine: chemical synthesis to clinical application. 1586 50

Hypobaric hypoxia (HBH) can produce neuropsychological disorders such as insomnia, dizziness, memory deficiencies, headache and nausea. It is well known that exposure to HBH cause alterations of neurotransmitters and cognitive impairment in terms of learning and memory. But the mechanisms are poorly understood. The present study aimed to investigate the cholinergic system alterations associated with simulated HBH induced cognitive impairment. Male Sprague-Dawley rats were exposed to HBH equivalent to 6100 m for 7 days in a simulation chamber. The cognitive performance was assessed using Morris Water Maze (MWM) task. Cholinergic markers like acetylcholine (ACh) and acetylcholinesterase (AChE) were evaluated in hippocampus and cortex of rats. Neuronal damage was also studied through morphological changes. Exposure to HBH led to impairment in relearning ability and memory retrieval and it was accompanied by decrease in ACh level and increase in AChE and led to morphological damage. Administration of AChE inhibitor (AChEI), physostigmine (PHY) and galantamine (GAL) to rats during HBH exposure resulted in amelioration of the deleterious effects induced by HBH. The AChEIs were able to improve the cholinergic activity by restoring the level of ACh by blocking the AChE activity. In addition, the AChEIs also prevented neurodegeneration by reducing the AChE level in cortical and hippocampal neurons.
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PMID:Acetylcholinesterase inhibitors enhance cognitive functions in rats following hypobaric hypoxia. 1944 92

Flupirtine is a centrally acting, non-opioid analgesic that is available in a number of European countries for the treatment of a variety of pain states. The therapeutic benefits seen with flupirtine relate to its unique pharmacological properties. Flupirtine displays indirect NDMA receptor antagonism via activation of potassium channels and is the first representative of a pharmacological class denoted the 'selective neuronal potassium channel openers'. The generation of the M-current is facilitated by flupirtine via the opening of neuronal Kv7 potassium channels. The opening of these channels inhibits exaggerated neuronal action potential generation and controls neuronal excitability. Neuronal hyperexcitability is a physiological component of many pain states such as chronic pain, migraine and neurogenic pain. Although large-scale clinical trials are lacking, the clinical trial database available to date from smaller-scale studies, together with extensive clinical experience, indicate that flupirtine effectively reduces chronic musculoskeletal pain, migraine and neuralgias, amongst other types of pain. In addition, flupirtine produces, at recommended clinical doses, muscle-relaxing effects in the presence of abnormally increased muscle tension. Its analgesic and muscle-relaxant properties were comparable to tramadol and chlormezanone, respectively, in two prospective trials in patients with lower back pain. Cytoprotective, anti-apoptotic and antioxidant properties have also been associated with flupirtine use in a small number of studies to date. When provided as combination therapy with morphine, flupirtine increases the antinociceptive activity of morphine 4-fold. Flupirtine displays superior tolerability when compared with tramadol and pentazocine. The most common adverse effects associated with flupirtine use are drowsiness, dizziness, heartburn, dry mouth, fatigue and nausea. With respect to its molecular structure, mechanism of action and adverse event profile, flupirtine is a unique drug. Flupirtine is an analgesic with many potential therapeutic benefits that may prove useful in the treatment of many disease states.
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PMID:Flupirtine in pain management: pharmacological properties and clinical use. 2083 97

Neuronal intranuclear inclusion disease (NIID) is a rare and slowly progressing neurodegenerative disease characterized by the presence of eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. Sporadic NIID case was more frequently encountered than familial. In our study, we reported two adult-onset NIID patients from a family and described their clinical, imaging, and pathological features. The first patient was a 61-year-old man who only presented with non-specific headache and dizziness; however, Brain MRI with diffusion-weighted images (DWI) sequence showed high-intensity signal involving a small regional portion of corticomedullary junction in the frontal and parietal lobe. The older sister of former, a 64-year-old female, who developed sudden onset of weakness of the right limb was admitted to our neurology department. Compared with the first patient, similar DWI high-intensity signal but more extensive area in the corticomedullary junction was found in her brain MRI examination, also prominent leukoencephalopathy in T2-weighted image. Significantly, skin pathology of the first patient showed that typical inclusions with strongly positive P62 and ubiquitin antibody could be seen in the nuclei of sweat gland cells, adipocytes, and fibroblasts. FMR1 gene was negative. Although rare, adult-onset NIID should be considered when the characteristic radiology changes of high intensity signal involving the corticomedullary junction in the brain DWI sequence was found. In addition, the pathological result of skin biopsy combined with negative genetic testing FMR1 or NOTCH2NLC can contribute to the accurate diagnosis of the disease. This article aims to improve the radiologists' knowledge of NIID by our cases presentation and reviewing literature.
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PMID:Neuronal intranuclear inclusion disease: two case report and literature review. 3283 83