Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042571 (vertigo)
 7,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of anti-vertigo drugs on medial vestibular nucleus (MVN) neurons were examined to assess the site and mode of action using cats anesthetized with alpha-chloralose. Single neuron activity in the MVN was extracellularly recorded using a silver wire microelectrode attached along a seven-barreled micropipette, each of which was filled with diphenhydramine, diphenidol, betahistine, glutamate or NaCl. Type I of the MVN neurons were identified according to the responses obtained when the animal placed on a turn-table was rotated sinusoidally. The effects of the drugs were examined on type I neurons which received impulses primarily from the labyrinth and sent them to the oculomotor nuclei. The microiontophoretic application of diphenhydramine, diphenidol and betahistine inhibited rotation-induced firing of type I MVN neurons. Diphenhydramine and diphenidol were more potent than betahistine. These results suggest that these drugs directly act on MVN neurons to reduce the responsiveness to rotatory stimulation.
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PMID:Effects of anti-vertigo drugs on medial vestibular nucleus neurons activated by horizontal rotation. 167 70

Flunarizine, a class IV Ca++ antagonist non-selective for slow Ca++ channels, has been shown to be beneficial in the prophylactic treatment of migraine, the treatment of vertigo, and as add-on treatment in therapy-resistant forms of epilepsy. Flunarizine protects the brain against functional and/or structural neuronal damage in various animal models of cerebral ischemia. In addition to its cerebrovascular effect, flunarizine has also direct neuroprotective actions. New data have emerged on flunarizine with regard to Ca++ and Na+ channels in neuronal cells. There are several possible mechanisms involved in the mode of action of flunarizine. Flunarizine may block Ca++ and Na+ channels, both of which may flux Ca++ as well as Na+. A decrease in Ca++ influx may prevent further release of glutamate, and activation of NMDA receptor gated Ca++ channels at physiological pH. A decrease in Na+ influx may prevent cytotoxicity secondary to a large gain in intracellular Ca++, by reverse operation of the Na+/Ca++ exchanger. This mechanism may be important when the glycolytic rate is increased with concomitant acidosis, and phospholipids are broken down as occurs typically during ischemia. Given the complexity of biochemical events leading to cell death, blocking exclusively one channel subtype is not likely to yield sufficient protection. Hence, it may be useful to develop anti-ischemic compounds which act on a series of pathways involved in Ca++ overload, rather than selectively block one such channel.
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PMID:Ca++ and Na+ channels involved in neuronal cell death. Protection by flunarizine. 185 Aug 15

The effects of 7% sodium bicarbonate on medial vestibular nucleus (MVN) neurons were examined to elucidate the mechanism underlying its anti-vertigo action, using alpha-chloralose-anesthetized cats. Intravenous injection of the drug at 1, 2 and 4 ml/kg every 10 min dose-dependently inhibited rotation- and glutamate-induced firing of type 1 neurons, although a low dose of the drug enhanced firing in a few neurons. However, microiontophoretic application of bicarbonate ions did not inhibit rotation- or glutamate-induced firing. After injection of the drug, the Po2 level in arterial blood did not differ from previous levels, but the bicarbonate ion levels dose-dependently increased concomitantly with an increase in pH, as compared with previous levels. These results suggest that the intravenous injection of 7% sodium bicarbonate directly inhibits the neuronal activity of the MVN, although the lower dose may enhance neuronal activity by acting on the peripheral vestibule.
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PMID:Inhibition by intravenously administered sodium bicarbonate of neuronal activity in medial vestibular nucleus neurons. 196 85

An electrophysiological study was performed to determine whether prednisolone hydrochloride directly influenced neuronal activities of the medial vestibular nucleus (MVN) in alpha-chloralose-anesthetized cats. Single neuronal activities of MVN were recorded extracellularly with a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. Each barrel was filled with prednisolone, glutamate, glutamic acid diethylester (GDEE) or CoCl2. Except for prednisolone, which was administered both intravenously and microiontophoretically, other chemicals were applied microiontophoretically to the immediate vicinity of the target neurons. These MVN neurons were classified as type I and II neurons according to their responses to horizontal and sinusoidal rotations. Intravenous prednisolone (up to 5 mg/kg) enhanced spontaneous and rotation-induced neuronal firings of both type I and II neurons in a dose-dependent manner. In a similar tendency, microiontophoretically applied prednisolone (50-200 nA) dose-dependently increased spontaneous and rotation-induced firings of both type I and II neurons. Microiontophoretic GDEE, a non-selective glutamate receptor antagonist, inhibited glutamate- and rotation-induced neuronal discharges without affecting prednisolone-induced increases in neuronal responses of MVN. In addition, iontophoretically applied CoCl2, a Ca2+ channel blocker, did not affect prednisolone-, glutamate- and rotation-induced neuronal findings of MVN. These results suggest that prednisolone induces excitation of type I and II neurons, probably by acting directly on the membrane of MVN neurons. Thus, glucocorticoids such as prednisolone may be effective for the treatment of vertigo resulting from hypofunction of vestibular nucleus neurons.
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PMID:Prednisolone excitation of medial vestibular nucleus neurons in cats. 759 71

Although glucocorticoids are sometimes used for the treatment of vertigo in certain disorders such as Meniere's disease, the mechanism underlying anti-vertigo effect remains unknown. The present study was performed to examine the effects of a glucocorticoid, dexamethasone, on neuronal activity in the medial vestibular nucleus (MVN) to determine whether or not the drug acts directly on the MVN neuron using alpha-chloralose-anesthetized cats which were fixed in a stereotaxic instrument placed on a turn-table. Single neuronal activities in the MVN were extracellularly recorded with a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. Each pipette was filled with dexamethasone phosphate (0.1 M), monosodium glutamate (1 M), glutamic acid diethylester (GDEE) (0.05 M: a non-selective glutamate receptor antagonist), CoCl2, (0.1 M: a non-specific calcium channel blocker), RU38486 (0.01 M: glucocorticoid receptor antagonist) or potassium canrenoate (0.1 M: a mineralo-cortical receptor antagonist). These chemicals were microiontophoretically applied to the immediate vicinity of the target neuron being recorded. The effects of the drugs were examined on type I neurons which were identified according to responses to rotation: the neuron showed an increase and a decrease in firing with ipsilateral and contralateral rotation to the recording site, respectively. Microiontophoretically applied dexamethasone (50-200 nA) dose-dependently increased spontaneous firing of MVN neurons. However iontophoretic application of GDEE did not affect the dexamethasone-induced increase in firing of the MVN neurons but inhibited glutamate- and rotation-induced firing. Microiontophoretically applied Co2+ did not affect dexamethasone-, glutamate- and rotation-induced firing. However, dexamethasone-induced firing was dose-dependently suppressed by iontophoretic RU38486, but not by canrenoate. Then a microdialysis study using alpha-chloralose-anesthetized cats was performed to determine whether or not dexamethasone affects the release of glutamate from vestibular nerve terminals. The microdialysis probe (CMA/10, 2 mm) was inserted into the MVN and perfused with Ringer solution at 2 ml/min. Samples were collected at 10-min intervals. Endogenous glutamate was measured using the HPLC-ECD method. When repetitive stimuli (200 microseconds duration, 0.5 mA and 5 Hz) were given to the vestibular nerve for 10 min, an increase in the release of glutamate was observed. Dexamethasone did not produce spontaneous or stimulation-induced release of glutamate. These results suggest that dexamethasone acts directly on the MVN neuron to excite neuronal activity through glucocorticoid receptors on neuron membranes, but the excitation is not due to the release of glutamate.
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PMID:[Excitatory effects of glucocorticoids on neuronal activity in the medial vestibular nucleus--mediation by glucocorticoid receptor on the membrane]. 791 23

Cinnarizine and flunarizine are piperazine derivatives with calcium antagonist and anticonvulsant properties and are used widely in the treatment of vertigo and circulatory disorders. They have been implicated recently in the aggravation, or even the induction, of parkinsonism in elderly patients. Because the aetiology of parkinsonism has been suggested as having a mitochondrial component, we have investigated the effects of both compounds on mitochondrial respiration and on the activities of the individual respiratory chain complexes. In intact mitochondria from rat liver, both drugs inhibited respiration rates, with substrates entering at Complex I (glutamate/malate) and Complex II (succinate). These effects could be explained by potent inhibitions (Ki 3-10 microM) of both complexes. Complex I is inhibited at a site near the ubiquinone-binding site, which is not competitive with respect to ubiquinone, whereas the inhibition of Complex II is apparently caused by competition with ubiquinone. Furthermore, the inhibition of NADH oxidation by flunarizine in submitochondrial particles caused an NADH-dependent generation of superoxide. These inhibitory properties of both compounds could be significant factors in the aggravation or induction of parkinsonism in elderly patients, in whom mitochondrial function already may be impaired.
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PMID:Flunarizine and cinnarizine inhibit mitochondrial complexes I and II: possible implication for parkinsonism. 830 75

To examine the relationship between neurosteroids and vertigo we performed electrophysiological studies to determine whether pregnenolone sulfate (PS) affects the activity of medial vestibular nucleus (MVN) neurons in alpha-chloralose-anesthetized cats. Single neuronal activities in the MVN were recorded extracellularly using a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. 3 mM PS, 1 M glutamate and 3 mM NaCl were applied microiontophoretically in the immediate vicinity of the target neurons. The effects of these drugs were then examined on type I and type II neurons, identified by their responses to horizontal and sinusoidal rotations. The iontophoretic application of PS dose-dependently increased the spontaneous firing of both type I and type II neurons. The larger increase in firing was observed in type I neurons as compared with type II neurons following the PS application. These results suggest that PS excites types I and II neurons differentially, presumably resulting in a disturbance of harmony of the vestibulo-ocular reflex with ensuing development of vertigo.
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PMID:The neurosteroid pregnenolone sulfate excites medial vestibular nucleus neurons. 965 6

The role of neuroprotective agents for maintaining or improving inner ear function, specifically for the symptom of tinnitus, is presented on the basis of neurootological, neurological, and neurosurgical clinical experiences. These clinical experiences involved the use of calcium channel blockers, free radical scavengers, corticosteroids, antagonists of glutamate at N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and various thrombolytic agents for the etiologies of ischemia, trauma, and hemorrhage. A pharmacological basis for such drug efficacy includes a property described as neuroprotection. A pathology-based protocol for drug selection is proposed for tinnitus control. The goal of this article is to introduce to the neurootologist or otologist and other professionals attempting tinnitus control neuroprotective drug therapies that are being applied to such central nervous system pathological processes as ischemia, trauma, hemorrhage, and neurodegeneration. The innovative application of such drug therapies for treating the symptom of tinnitus of the severe disabling type is considered. The use of neuroprotective drugs in intratympanic drug therapy via the round window, for treatment of inner ear complaints of hearing loss, tinnitus, and vertigo, is discussed.
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PMID:Neuroprotective Drug Therapy: A Medical and Pharmacological Treatment for Tinnitus Control. 1075 68

Nitric oxide (NO)-mediated neurotoxicity may be an appropriate pathophysiological model with which to explain a variety of inner ear diseases characterized by acute or progressive hearing loss, tinnitus and vertigo. The localization of NO synthase (NOS) isoforms was examined in the inner ear of the pigmented guinea pig after intratympanic injection of 1 mg lipopolysaccharide (LPS) or 5 mg gentamicin (GM) using an immunohistochemical method, revealing the expression of NOS II in the inner ear. Production of NO in the isolated organ of Corti and utricle or in the isolated vestibular and cochlear hair cells after stimulation with L-arginine, glutamate, GM and LPS was investigated using the fluorescence indicator 4,5-diaminofluorescein diacetate. The fluorescence intensity of the sensory cells was augmented by stimulation with L-arginine, glutamate, GM and LPS. A significant increase in NO production was also noted in the LPS-treated animals. These findings imply that NO from constitutive NOS may mediate ototoxicity in the early phase, whereas NO from NOS II may contribute to the late phase of tissue damage in the inner ear. Based on this hypothesis, reduction of glutamatergic excitotoxicity and inhibition of NOS, scavenging superoxide and scavenging peroxynitrite are thought to attenuate NO-mediated otoneurotoxicity.
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PMID:Pharmacological models for inner ear therapy with emphasis on nitric oxide. 1127 Apr 88

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with the fatal evolution. Recent studies in knowledge of the pathogenic mechanisms underlying ALS showed that the excitotoxicity has an important role in the neurodegeneration. The riluzole, an antagonist of glutamate, is the first drug approved by FDA for the treatment of patients with ALS. The efficacy of riluzole (dose recommended 50 mg twice a day) in prolonging the survival of patients with ALS has been demostrated in two principal controlled clinical trials. The most frequent adverse events related to riluzole treatment were: nausea, vomiting, anorexia, diarrhea, asthenia, somnolence, vertigo, circumoral paresthesia, abdominal pain and dizziness. Some events tend to be related to the dose: vertigo, diarrhea, nausea, circumoral paresthesia and anorexia appear more frequently with 200 mg/die that with lower dose. Generally with tree months from the beginning of the treatment with riluzole, an increase serum transaminase levels has been noted; mostly transient and regressing after two-sex months of treatment. A monitoring of serum transaminase levels is suggested during the first year of treatment with riluzole The clinical studies shows that the adverse events produced by riluzole are mostly reversible and dose-dependent, this demostrates a satifying profile of tolerability of the drug. Anyway, a deeper knowledge of its tolerability may lead us to a better use of riluzole, avoiding in this way the interruption of treatment.
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PMID:[Tolerability of riluzole: a review of the literature]. 1514 78


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