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)

Chronic bipolar electrodes were implanted in cortical, limbic, diencephalic and mesencephalic regions of the rat. Following recovery from surgery the rats were maintained for 14--26 days on a liquid diet in which 35--42% of total calories were provided by ethanol. Following ethanol withdrawal, electrographic and behavioral monitoring was continued for 8--10 h. The withdrawal of ethanol resulted in the time-dependent appearance of a variety of withdrawal signs including tail arching, ataxia, rigidity, tremor and spontaneous and audiogenic convulsions. These behavioral signs were accompanied by the development of epileptiform abnormalities across wide-spread brain regions. Analysis of preconvulsive spike activity revealed a greater spike frequency in limbic, mesencephalic and non-specific diencephalic regions, as compared to those in cortex and specific diencephalon. Seizure discharge during the tonic-clonic phase of the primary audiogenic convulsion was initiated in the mesencephalon or amygdala, but spread rather extensively to the remainder of the brain. In those instances, however, where multiple convulsions occurred following the audiogenic convulsions, there was a marked decline in spread of seizure discharge to the cortex. These results were interpreted to support the notion that some degree of neuroanatomical specificity exists in the genesis of epileptiform abnormalities during ethanol withdrawal. A comparison of these results with those studying the neural mechanisms underlying other forms of generalized epilepsy was made. It is hypothesized that central pacemaking regions such as medial thalamus or reticular formation may serve to organize isolated epileptiform activity into coherent patterns of paroxysmal activity throughout the brain during the ethanol withdrawal syndrome.
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PMID:Ethanol dependence in the rat: role of non-specific and limbic regions in the withdrawal reaction. 8 50

Periodic brain stimulation, particularly in the limbic system, at stimulus intensities initially too low to produce any behavioural or EEG effects, progressively produces EEG changes, motor automatisms, and eventually convulsions, an effect called kindling. Data are presented and reviewed that suggest that the severity of alcohol withdrawal symptoms progressively increases over years of alcohol abuse in a stepwise fashion similar to the kindling process. The model is presented that the limbic system hyperirritability which accompanies each alcohol withdrawal serves over time to kindle increasingly widespread subcortical structures. These long-term changes in neuronal excitability might relate to the progression of alcohol withdrawal symptoms from tremor to seizures and delirium tremens, as well as the alcoholic personality changes between episodes of withdrawal.
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PMID:Kindling as a model for alcohol withdrawal syndromes. 35 67

Three major metabolites (M1, M2, M3) of nomifensine (8-amino-1,2,3,4-tetrahydro-2-methyl-4-phenyl-isoquinoline) are formed by hydroxylation and methoxylation of the phenyl ring. They were compared with nomifensine 1. in various psychopharmacological tests in vivo, carried out in mice after oral or i.p. treatment and 2. in neurochemical in vitro studies, measuring inhibition of noradrenaline (NA), dopamine (DA), and serotonin (5-HT) uptake in rat brain synaptosomes. M1 (4'-hydroxy-nomifensine) was the most active metabolite, while M2 and M3 had little or no effect in pharmacological tests. M1 reversed reserpine hypothermia in doses greater than 2.5 mg/kg, antagonized tetrabenazine catalepsy (ED50 68 mg/kg) and reversed oxotremorine hypothermia (ED50 33 mg/kg). In these tests nomifensine was also active, being about 3-10 times more potent than M1. In contrast to nomifensine M1 had also serotoninergic activity, potentiating both phenelzine-induced twitching (ED50 11 mg/kg) and the anticonvulsant effect of 5-hydroxytryptophan. Moreover, M1 prolonged the hexobarbital sleeping time in doses greater than 10 mg/kg, prevented nicotine-induced convulsions (ED50 58 mg/kg) and reduced the oxotremorine tremor (ED50 59 mg/kg). The LD50 of M1 was 1100 mg/kg orally. In vitro M1 was equipotent with nomifensine in inhibiting DA uptake (IC50 1.5 x 10(-7) M) and twice as active in inhibiting NA uptake (IC50 1.1 x 10(-8) M). In contrast to nomifensine M1 was also a potent inhibitor of 5-HT uptake (IC50 3.3 x 10(-7) M). M2 and M3 were less active than M1 in all experiments.
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PMID:Pharmacological and biochemical studies with three metabolites of nomifensine. 40 62

An extrapyramidal disorder occurring in three generations of a family (only males) is described The clinical features were progressive dementia and extrapyramidal signs without choreiform hyperkinesia. The youngest patient (onset of disease at the age of 22 years) showed tremor, rigidity, ataxia, convulsions, and myoclonus. The neuropathologic findings were characterized by isolated symmetrical degeneration of the corpus striatum and diffuse cortical atrophy without affecting other cerebrospinal neuronal systems. The clinical features of this familial disorder and its relation to other types of familial striatal degeneration and to the juvenile form of Huntington's chorea are discussed.
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PMID:[Familial striatal degeneration (author's transl)]. 54 75

Since it had been demonstrated that L5418 has an anti-convulsant effect with no relation to its anti-inflammatory properties, comparative studies were carried out with the use of currently available anti-convulsant agents as controls. L-5418 inhibited tonic convulsions induced by maximal electroshock and strychinine in mice and prevented animals from the death sequence. L-5418 had an inhibitory effect on tonic convulsions induced by pentetrazol and N-sulfamoyl-hexahydroazepine (SaH 41-178), but not on clonic convulsions by those compounds at even a high dosage or on clonic convulsions induced by picrotoxin and bemegride. Trimethadione produced an inhibitory effect on both tonic and clonic convulsions. The hypnotic agents, phenobarbital and glutethimide inhibited both convulsions, but a higher dose was required in the case of clonic convulsions. Anti-convulsant agents are classified into three different groups according to their mode of action. L-5418 had the same mode of action as seen with diphenylhydantoin and carbamazepine. As L-5418 did not inhibit tremor induced by tremorine, an anti-Parkinson effect was ruled out. When L-5418 was administered alone, the animals did not lose the righting reflex nor show muscle relaxation observed in inclined screen and rotarod tests. Moreover, the compound had no influence on the aggressive behavior induced by electrical stimulation or olfactory bulb ablation. L-5418 possesses a selective anti-convulsant effect, yet has no sedative, tranquilizing or disturbing effects on movement such as equilibrium disturbance or muscle relaxation. L-5418 may prove useful for grand mal epilepsy as it is less toxic than diphenylhydantoin and carbamazepine.
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PMID:Anti-convulsant effect of phthalazino-2,3b-phthalazine-5(14H),12(7h)-dione (L-5418). I. Behavioral effect. 56 46

Estonian shale oil contains about 25--30% phenols, and their action determines the toxicity of shale oils. The clinical symptoms of intoxication are rather similar, regardless of route of administration. Due to neurotropic action, the coordination of movements is impaired, and clonic and tetanic convulsions, paresis and paralysis of extremities, and narcosis are observed. In subacute and chronic toxicity tests, dysfunction of the central nervous system was found. In long-term (4--6 month) experiments, changes in liver and kidney function were found. Shale oil has gonadotropic activity and causes changes in the sexual cycle as well as diminution of the number of primordial folicles in the ovaries or a decrease in the quantity of normal spermatogonia in testicular germinal epithelium. Shale oils produce local irritation of skin and mucous membranes. Shale oil can induce sensitization of the organism after repeated administration. The results of acute intoxication tests have proved that volatile and nonvolatile phenol fractions, isomeric dimethylphenols, and 5-methylresorcinol, must be characterized as moderately toxic substances; the LD50 ranges from 501 to 1500 mg/kg. The clinical symptoms of acute toxication are similar for all studied phenols (restlessness, unsteadiness, clonic tremor, paresis and paralysis of extremities, and death). In spite of the moderate toxicity of phenols in acute experiments, repeated administration of small doses can cause different changes in the nervous system and internal organs of experimental animals. For all the phenols studied, the maximum allowable concentration in water was limited by their effect on the organoleptic properties of water. The nonactive dose for warm-blooded animals is from 100 to 3000 times the threshold limit value of phenols on the basis of their organoleptic properties. The effect of commercial products of oil shale industry is generally determined by the toxicity of the main components: water-soluble oil shale phenols.
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PMID:Toxicological studies of shale oils, some of their components, and commercial products. 57 2

The acute toxicity of 6-(3-[4-(o-methoxyphenyl)-1-piperazinyl-propylamino)-1,3-dimethyluracil (urapidil, Ebrantil) was tested in rats and mice using oral and intravenous routes. The tolerance upon repeated oral administration was tested in subacute and chronic toxicity studies lasting 3 weeks, 3, 6 and 12 months in the rat, as well as studies lasting 4 weeks and 6 months in the dog. The effect of urapidil on the reproduction in mice, rats and rabbits was also investigated. Sedation is seen in mice and rats after a single administration of urapidil, at lethal doses, tremor and convulsions appear. The same symptoms were seen in experiments with repeated oral administration in the rat (stomach tube) or in the dog (tablets) as the criterium of tolerance. In feeding studies in the rat, the decreased body weight gain was the criterium of toxicity. The no-effect dose in the rat is 42 times the therapeutic dose in man. The no-effect dose in the dog lies between 8 and 21 times the average therapeutic dose. An inhibition of the estrus cycle in the rat proved to be species-specific. In reproductin studies, significant toxic effects were seen besides functional disturbances specific to the rat. Urapidil was not teratogenic. The development and reproductive capacity of the F1-generation was not affected.
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PMID:[Toxicologic study on the antihypertensive agent urapidil]. 57 2

The effect of chlorophenothane (pp'--DDT) and five structurally related compounds op-DDD (op'-DDD, pp'-DDD, DTE, DCMP and DCP see text) on the cerebral hemisphere gamma-aminobutyric acid (GABA), the main inhibitory transmitter in brain contents and possible correlation with central activities was demonstrated in rats. The tested compounds were given in oral doses of 600 mg/kg in peanut oil. Cerebral GABA content was determined 1, 3 and 6 hrs after the ingestion of pp'-DDT and 3 hrs after each of the other drugs. The mean GABA content in each group of rats was compared with control groups, either without any treatment, or receiving the equivalent volume of peanut oil. pp'-DDT produced a significant reduction in brain GABA contents 3 and 6 hrs after its administration. This was accompanied by excitability, tremor and clonic convulsions. Of the congenors, only DTE exerted a similar effect. The present results point to the possibility of partial involvement of GABA in the tremor and convulsions induced by pp'-DDT. They also indicate the importance of the CCl2 grouping in the molecule for the induction of central effects of pp'-DDT.
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PMID:Investigation of the effect of chlorophenothane and certain chemically related compounds on the cerebral gamma-aminobutyric acid contents in rats. 74 May 48

The effect of varying the pressure/time profile upon development of tremors and convulsions of the high-pressure neurological syndrome was studied in adult mice and squirrel monkeys and in baby mice. Two distinct response patterns were observed. In the adults rapid compression produces early onset of convulsions; convulsions subside rapidly when animals are held at constant pressure just above the convulsion point; and interrupted compression schedules show that total compression time rather than instantaneous compression rate at the moment seizures develop is the controlling parameter. Baby mice up to 12 days of age, by contrast, fail to show any perceptible relation between compression rate and convulsion threshold pressure (Pc); their seizures continue for a considerable period of time after a constant pressure level just above the convulsion threshold has been reached; and interrupted compressions of type a fail to change their convulsion threshold. Together with supplementary data regarding tremor thresholds and the transient increase of convulsion thresholds by prior seizures these results lead to a proposed schema describing these phenomena in terms of a pressure-dependent primary event predisposing to tremors and convulsions; a time-dependent event counteracting the convulsions (absent in baby mice); and a transient effect of prior convulsions, raising subsequent Pc.
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PMID:Rate factors in development of the high-pressure neurological syndrome. 80 65

Inbred Swiss mice were treated with technical DDT (1) orally with the diet or by intubation; (2) subcutaneously and (3) by skin painting. The total duration of the experiment was 80 weeks. There was no difference in body growth and mortality between the experimental and control groups. Toxic manifestations of DDT were observed in treated mice in the form of tremor, convulsions and corneal opacity usually after 40 weeks. Oral and subcutaneous DDT treatment resulted in a significant increase in the incidence of tumours mainly of lymphoid tissues, lung and liver. The highest tumour incidence was recorded in the group of mice receiving DDT by subcutaneous injections. Males and females were equally susceptible. No evidence of carcinogenicity was observed in the painted group.
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PMID:Carcinogenicity of DDT (dichlorodiphenyl trichloroethane) in pure inbred Swiss mice. 86 49


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