Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of verapamil and flunarizine on phencyclidine-induced effects has been studied in adult male rats. Both verapamil (25 and 100 micrograms/10 microliters, i.c.v.) and flunarizine (40 and 60 mg/kg, i.p.) significantly reduced behavioural (mean intensity of ataxia, mean duration of head weaving) and the EEG (increase in the mean voltage of background activity of the EEG) effects induced by phencyclidine 5 mg/kg (i.p.). It was reported previously that nimodipine and diltiazem significantly potentiate effects induced by phencyclidine. The contrasting results obtained with verapamil and flunarizine, suggest that these drugs may modulate effects induced by phencyclidine by acting at sites other than NMDA receptor-coupled "L"-type calcium channel.
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PMID:Verapamil and flunarizine inhibit phencyclidine-induced effects: an EEG and behavioural study in rats. 147 25

The effects of the dihydropyridine calcium antagonist, nitrendipine and the calcium channel activator, Bay K 8644, have been compared on the anaesthetic, ataxic and anticonvulsant effects of benzodiazepines. Possible interactions between the peripheral benzodiazepine receptor antagonist, PK11195, and the classical benzodiazepines were also examined. Nitrendipine considerably potentiated the anaesthetic effects of benzodiazepines and increased their ataxic effects but had no effect on the anticonvulsant actions. Clonazepam did not produce anaesthesia, at doses up to 1 g kg-1 or when given with nitrendipine. When given alone, nitrendipine did not cause general anaesthesia. Nitrendipine did not appear to alter the metabolism of midazolam. The calcium channel activator, Bay K 8644, reduced the anaesthetic potency of midazolam and, when given alone, produced ataxia. It did not significantly alter central concentrations of midazolam. The "peripheral" benzodiazepine antagonist, PK11195, did not affect the ataxic or anaesthetic actions of benzodiazepines. These results suggest that dihydropyridine-sensitive calcium channels may be more important to the general anaesthetic than to the anticonvulsant actions of benzodiazepines. The "peripheral" benzodiazepine site did not appear to play a role in either of these properties.
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PMID:Differential interactions between benzodiazepines and the dihydropyridines, nitrendipine and Bay K 8644. 171 26

Effects of organophosphorus esters (OPs) inducing delayed neuropathy in the adult hen have traditionally been evaluated by assessment of morphology and function of nerve and muscle in the rear limbs of animals exposed. In this study, organophosphorus-induced delayed neuropathy (OPIDN), including neuromuscular function and histology, were studied in vivo using sciatic nerve, tibial nerve and gastrocnemius muscle in anesthetized hens that had been administered phenyl saligenin phosphate (PSP), 2.5 mg/kg by intramuscular injection. In addition, OPIDN was examined in vitro using the biventer cervicis nerve and muscle of the same adult hens. Both nerve-muscle preparations were used for construction of strength duration curves (SDC) on days 4-5, 7-8, and 15-16 after PSP; the biventer cervicis preparation was also used 21-22, 37 and 64 days after PSP administration. Histological examination was done at these same time periods. SDC revealed significant increases in excitability thresholds for preparations from hens receiving PSP only compared to preparations from control hens, or compared to preparations from hens treated with PSP and either nifedipine (1 mg/kg intramuscularly for 5 days), or verapamil (7 mg/kg intramuscularly for 4 days), with treatment beginning 24 hours before administration of PSP. Ataxia, which appeared 7-10 days after hens were given PSP, was less pronounced in hens given PSP plus either calcium channel blocker than in hens given PSP alone. Whether treatment was initiated before or after PSP, verapamil, a phenylalkylamine, reduced sensitivity of the biventer cervicis muscle to acetylcholine-induced stimulation. The dihydropyridine, nifedipine, was less effective at reducing muscle sensitivity to acetylcholine post-exposure than when used as a pretreatment. Lesions were extensive in the biventer cervicis nerve after PSP administration and modification by treatment with calcium channel blockers was evident.
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PMID:Modification of phenyl saligenin phosphate-induced delayed effects by calcium channel blockers: in vivo and in vitro electrophysiological assessment. 208 84

Radiation induced white matter necrosis in the rat spinal cord is preceded by changes in permeability of the blood brain-barrier, reduced blood flow, and infarction so that the necrosis is an ischemic necrosis. Attempts have been made to modify this developing pathology by the administration of drugs post-irradiation but just prior to the changes in vascular permeability. Verapamyl, a calcium channel blocker, had no effect on the development of ataxia. Dipyridamole, a drug which increases blood flow and reduces thrombosis, delayed and reduced the onset of ataxia. A low iron diet and desferrioxamine which reduces reperfusion injury also delayed and reduced ataxia. These results support the thesis that vascular changes are an important pathway in the development of radiation necrosis and that reperfusion injury is an important factor in the development and exacerbation of radiation damage to the spinal cord.
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PMID:The reduction of radiation damage to the spinal cord by post-irradiation administration of vasoactive drugs. 237 Jan 94

Verapamil, a calcium channel blocker, was administered to adult white leghorn hens to determine if inhibition of calcium entry could alter delayed neuropathy induced by administration of phenyl saligenin phosphate (PSP). Verapamil was given im in doses of 7 mg/kg/day for 4 days beginning 24 hr before administration of PSP (2.5 mg/kg im). Ataxia was less pronounced in hens given PSP plus verapamil than in hens given PSP alone during observations made 8-28 days after PSP administration. Myelinated fiber lesions were less extensive and regeneration more notable in the biventer cervicis nerve in chickens given PSP plus verapamil, with samples obtained both 17 and 28 days after PSP. In the absence of verapamil, rheobase and chronaxie values of strength-duration curves were higher and shorter, respectively, and sensitivity to acetylcholine was increased in biventer cervicis nerve-muscle preparations from hens given PSP. Verapamil did not alter PSP-induced inhibition of neurotoxic esterase, indicating that the mechanism involved in amelioration of these indices of delayed neuropathy was not associated with initial enzyme inhibition caused by this organophosphorus ester.
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PMID:Effect of verapamil on organophosphorus-induced delayed neuropathy in hens. 255 27

Mice injected with the calcium agonist BAY K 8644 (2-4 mg/kg, i.p.) displayed profound behavioral changes including ataxia, decreased motor activity, Straub tail, arched back, limb clonus and tonus, and an increased sensitivity to auditory stimulation. BAY K 8644 significantly impaired rotorod performance in mice with an ED50 of 0.8 mg/kg. The behavioral effects of BAY K 8644 were antagonized by nifedipine, but not by the non-dihydropyridine calcium channel antagonist verapamil or the alpha-adrenoceptor antagonist prazosin. Further, the actions of BAY K 8644 were not mimicked by the alpha-adrenoceptor agonist methoxamine at doses up to 4.5 mg/kg. These observations, coupled with the findings that BAY K 8644 is a potent, competitive inhibitor of [3H]nitrendipine binding to the dihydropyridine binding site in mouse brain (Ki = 7.0 X 10(-9) M), suggests that BAY K 8644 may produce its behavioral actions via an interaction with the DHP binding site, which has been linked to the control of calcium flux across membranes in peripheral tissues.
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PMID:The behavioral effects of the calcium agonist Bay K 8644 in the mouse: antagonism by the calcium antagonist nifedipine. 258 Nov 45

Treatment of rats with the central thiamine antagonist, pyrithiamine, results in severe neurological symptoms such as ataxia and convulsions. Induction of proto-oncogene c-fos expression, often related to seizure activity, has been detected in the brains of thiamine-deficient rats by means of Northern blot analysis and in situ hybridization. Region-selective increases of lactate observed following thiamine deficiency development are largely coincident with histologically vulnerable regions. When thiamine-deficient rats were treated with the calcium channel blocker, nicardipine, lesions associated with thiamine deficiency did not appear and there was no induction of c-fos mRNA expression. This suggests a neurocytoprotective role of nicardipine to neuronal cell damage in thiamine-deficient encephalopathy.
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PMID:Proto-oncogene c-fos induction in thiamine-deficient encephalopathy. Protective effects of nicardipine on pyrithiamine-induced lesions. 822 66

Mutations at the mouse tottering (tg) locus cause a delayed-onset, recessive neurological disorder resulting in ataxia, motor seizures, and behavioral absence seizures resembling petit mal epilepsy in humans. A more severe allele, leaner (tg(la)), also shows a slow, selective degeneration of cerebellar neurons. By positional cloning, we have identified an alpha1A voltage-sensitive calcium channel gene that is mutated in tg and tg(la) mice. The alpha1A gene is widely expressed in the central nervous system with prominent, uniform expression in the cerebellum. alpha1A expression does not mirror the localized pattern of cerebellar degeneration observed in tg(la) mice, providing evidence for regional differences in biological function of alpha1A channels. These studies define the first mutations in a mammalian central nervous system-specific voltage-sensitive calcium channel and identify the first gene involved in absence epilepsy.
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PMID:Absence epilepsy in tottering mutant mice is associated with calcium channel defects. 892 30

A polymorphic CAG repeat was identified in the human alpha 1A voltage-dependent calcium channel subunit. To test the hypothesis that expansion of this CAG repeat could be the cause of an inherited progressive ataxia, we genotyped a large number of unrelated controls and ataxia patients. Eight unrelated patients with late onset ataxia had alleles with larger repeat numbers (21-27) compared to the number of repeats (4-16) in 475 non-ataxia individuals. Analysis of the repeat length in families of the affected individuals revealed that the expansion segregated with the phenotype in every patient. We identified six isoforms of the human alpha 1A calcium channel subunit. The CAG repeat is within the open reading frame and is predicted to encode glutamine in three of the isoforms. We conclude that a small polyglutamine expansion in the human alpha 1A calcium channel is most likely the cause of a newly classified autosomal dominant spinocerebellar ataxia, SCA6.
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PMID:Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. 898 70

Tottering and leaner, two mutations of the mouse tottering locus, have been studied extensively as models for human epilepsy. Here we describe the isolation, mapping, and expression analysis of Cacnl1a4, a gene encoding the alpha subunit of a proposed P-type calcium channel, and also report the physical mapping and expression patterns of the orthologous human gene. DNA sequencing and gene expression data demonstrate that Cacnl1a4 mutations are the primary cause of seizures and ataxia in tottering and leaner mutant mice, and suggest that tottering locus mutations and human diseases, episodic ataxia 2 and familial hemiplegic migraine, represent mutations in mouse and human versions of the same channel-encoding gene.
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PMID:Mutations in the Cacnl1a4 calcium channel gene are associated with seizures, cerebellar degeneration, and ataxia in tottering and leaner mutant mice. 906 Apr 10


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