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

Administration of 10 mg/kg TRH to mice was found to reduce the sleep and hypothermia induced by 4.7 g/kg ethanol. However, TRH did not reduce the sleep of mice that were given gamma-hydroxybutyric acid (GHBA), baclophen, or aminooxyacetic acid (AOAA) in combination with 3 g/kg/ ethanol. TRH also failed to reverse the hypothermia induced by the combination of ethanol and baclophen or GHBA, and the characteristic neurological effects of TRH e.g. tremor, increased muscle tone, and increased respiratory rate were reduced. In addition, TRH-induced locomotor stimulation was prevented by pretreatment with small doses of the GABA-ergic agents, and while 30 mg/kg TRH reduced the hypothermia produced by large doses of the GABA-ergic drugs, it did not antagonize the locomotor retardation produced by baclophen or GHBA. A hypothesis that the analeptic effects of TRH may be medicated via an inhibition of GABA systems is discussed.
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PMID:Antagonism of the analeptic activity of thyrotropin-releasing hormone (TRH) by agents which enhance GABA transmission. 1 50

The effect of piracetam, a cyclical derivative of GABA, was compared with that of a placebo in a double-blind study of 60 patients with post-concussional syndrome of 2-12 months' duration. The daily dose of piracetam was 4,800 mg. After 8 weeks of treatment piracetam significantly reduced the occurrence and severity of the following symptoms: vertigo, headache, tiredness, decresed alertness, increased sweating and neurasthenic symptoms. No significant effect was observed on the following symptoms: tremor, orthostatic symptoms, and memory disorders. Side effect were reported by 64% of the patients under piracetam and by 32% under placebo. In the author's opinion, piracetam seems to be a promising new drug for the treatment of post-concussional syndrome.
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PMID:Piracetam in the treatment of post-concussional syndrome. A double-blind study. 34 47

In our previous work we examined the mechanism of action of the new tremorogenic substance verruculogen isolated by Cole and coworkers. Examining the effect of various substances with known mechanisms of action on verruculogen-induced tremor, we concluded that this tremor was probably related to decrease of GABA levels in CNS. In order to further define the mechanisms of action of verruculogen, we determined brain GABA levels in animals in which tremor was produced by verruculogen administration. Verruculogen administration produced a decrease in GABA levels in mouse CNS. This finding substantiates our earlier suggestion that verruculogen-induced tremor is mediated by a loss of inhibitory GABA function.
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PMID:Verruculogen: a new substance for decreasing of GABA levels in CNS. 93 44

Glycine and GABA administered intraventricularly and intrastriatally were found to inhibit the oxotremorin tremor in rats. The two amino acids reduce both the spontaneous release of acetylcholine into the ventricle and the discharge measured under oxotremorin treatment. The inhibition of the tremor and of acetylcholine release can be blocked by amino acid antagonists (strychnine and picrotoxin), whose effects are not specific for one of these amino acids; this action can be interpreted as effect of interference with other central transmission systems. Structures located close to the ventricles (nigrostriatal path ways) are discussed as possible points of action.
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PMID:[Effect of various amino acids and their antagonists on the cholinergic tremor and acetylcholine release in the CNS of the rat]. 122 39

To study MPTP-induced muscular rigidity, we try to detect the changes of both dopamine (DA) and GABA within rat striatums by immunohistochemical means. A high dose (30 mg/kg) of MPTP i.p. injected into rats produces behavioral abnormalities (tremor and ataxia), and higher doses (greater than 60 mg/kg) develop an acutely muscular rigidity without producing a measurable histological change. GABA is induced in the striatum of 4 MPTP (30 mg/kg) i.p. treated-rats developed tremor and ataxia. But the animals recovered to an apparently normal state and are not showed GABA-immunoreactivity. Dense GABA-immunoreactivity is observed in the striatum developed muscular rigidity, when the animals are injected with 60 mg/kg MPTP i.p.. At this time, their striatums show slight decrease of DA-immunoreactivity in medium sized-spiny neurons. The results give some insight as to how DA and GABA function within the striatum with respect to the development of neuronal abnormalities. It is also suggested by our behavioral and immunohistochemical studies that effects induced by the depletion of DA within the striatum may be mediated through the inhibition of the striato-nigral GABAergic pathway, which in turn may lead to an activation of the nigrothalamic or nigro-collicular GABAergic pathway. This study indicates that the role of striatal GABAergic transmission is important in the development of muscular rigidity. The activity within the striatum can be followed with immunohistochemical technique for GABA morphologically.
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PMID:Immunohistochemical detection of GABA in rat striatum by intraperitoneal injection of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). 180 45

The transport system of taurine was investigated in fragments of goldfish retina prepared from the total tissue and from concentric regions: center and periphery. A high-affinity, saturable, sodium-dependent system was demonstrated in the three types of fragments. The Km for one-site analysis was similar in the two regions and the total retina. The analysis for two sites revealed a significant higher Km for the high-affinity site in fragments from the central region. The maximal uptake rate was higher in the central zone than in the total retina or the periphery. The Hill slopes obtained from saturation experiments of fragments of total retina, center, and periphery were similar to one other and near to 1. The slope of the time course uptake was intermediate for total retina and higher in the center than in the periphery. Hypotaurine and beta-alanine were found to inhibit taurine uptake, but GABA was a weak inhibitor. The values of Ki for hypotaurine by one- and two-site analysis were lower in the central region. The disruption of photoreceptors by shaking did not modify significantly the uptake of the amino acid. Remotion of endogenous taurine by dialysis of central and peripheral fragments increased the uptake in the periphery, but not in the center. The differences observed among the three samples revealed less affinity and high capacity for taurine uptake in the center, plus a higher sensitivity of inhibition. In addition, the peripheral zone had a greater affinity for taurine, and the maximal velocity of the entrance seems to be inhibited by the higher concentration of the amino acid in this zone. These observations may reflect differences between proliferating and non-proliferating regions of the retina (i.e., periphery and center).
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PMID:Differential taurine uptake in central and peripheral regions of goldfish retina. 190 45

The chronic administration of theophylline was studied in twenty patients with essential tremor in a double-blind cross-over trial. The tremor was improved significantly after four weeks of treatment. In mice the chronic administration of theophylline was compared with propranolol on the modulation by adenosine, 5-HT, (-)isoprenaline or GABA of NMDA-induced depolarisation of neocortical slices. Adenosine depolarisation was abolished by two-weeks treatment with theophylline but not propranolol. Potentiation by (-)isoprenaline of NMDA responses was reduced by theophylline (100 mg/kg/day) and propranolol treatment (25 mg/kg/day), but a lower dose of propranolol further increased it. The enhancement by 5-HT of NMDA-induced depolarisation was unaffected by the pretreatment with theophylline, while the higher dose of propranolol blocked it. GABA caused no significant change of NMDA depolarisation in control slices, but after theophylline treatment (100 mg/kg/day) and propranolol administration at both doses it significantly potentiated NMDA depolarisation. The enhancement of GABA sensitivity might be an important common factor in decreasing the essential tremor after propranolol and theophylline treatment.
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PMID:The effect of theophylline on essential tremor: the possible role of GABA. 194 76

Withdrawal of rats from 5 weeks of a liquid ethanol diet (10%), resulted in anxiogenic responses in the social interaction and elevated plus-maze tests of anxiety. The rats withdrawn from ethanol also showed increased aggression, tremor and rearing. Baclofen (1.25 and 2.5 mg/kg), but not nitrendipine (25-100 mg/kg), reversed the anxiogenic withdrawal responses, without having any effect in control animals and without having significant sedative effects. Baclofen reduced the enhanced aggression during withdrawal of ethanol, but this may have reflected a more general anti-aggressive action. Baclofen (2.5 mg/kg) reduced the withdrawal tremor. Nitrendipine (100 mg/kg) significantly reduced withdrawal tremor, but this dose was sedative, so this was likely to be a non-specific effect. It is proposed that the anxiogenic response during withdrawal of ethanol is due to a reduced GABA function, involving both GABAA and GABAB receptors.
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PMID:Effects of baclofen and nitrendipine on ethanol withdrawal responses in the rat. 203 Aug 22

The GABA/benzodiazepine receptor complex in the basal ganglia of primates treated with the neurotoxin n-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been studied by semi-quantitative autoradiography with [3H]flunitrazepam ([3H]FNZ). Systemic treatment with MPTP produced a stable and lasting parkinsonian condition, with pronounced bradykinesia, akinesia and tremor. In the lateral segment of the globus pallidus (GPL) there was a significant reduction of [3H]FNZ binding compared with non-treated animals. There were no significant changes in the [3H]FNZ binding in the caudate nucleus, putamen and medial globus pallidus (GPM). This suggests that MPTP-treatment increases GABA release within the GPL exclusively. In view of the available evidence suggesting increased striatal output, and reduced unit activity within the GPL of the MPTP-treated primate, it seems likely that the striatal GABAergic output to the GPL is overactive in this model of Parkinson's disease. Furthermore, as there is no evidence for a change in GABA function within the GPM using this measure, the striatal neurones which innervate the GPM may be differentially affected by loss of dopamine innervation. In line with structural evidence and extrastriatal dopamine receptor distribution this suggests that the two striatopallidal systems are functionally heterogeneous. A hemi-parkinsonian primate model has also been used in this study. This model was produced by injection of MPTP directly into one carotid artery. The substantia nigra pars compacta (SNc) was destroyed on the injected side alone, and consequently the appearance of parkinsonian symptoms was confined to the contralateral side. [3H]FNZ binding in the GPL appears to be bilaterally reduced in this model, suggesting an interaction between the treated and non-treated side of the brain. In addition there is increased binding in the putamen and GPM with respect to the non-treated side of the brain. The increased [3H]FNZ binding in the GPM of the unilateral model may be due to the greater disruption of the nigropallidal and/or nigrostiatal dopamine neurones relative to the systemic model. The former would have the effect of uncoupling D1 dopamine receptors located on the terminals of striatal efferents from nigropallidal dopamine input, and as D1 dopamine receptors are implicated in the presynaptic control of GABA release from the terminals of striatal efferents, this would consequently reduce the level of GABA release in the GPM. The latter possibility would suggest that striatopallidal neurones projecting to GPM are more resistant to the effects of dopaminergic denervation than those projecting to GPL.
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PMID:The role of striatopallidal neurones utilizing gamma-aminobutyric acid in the pathophysiology of MPTP-induced parkinsonism in the primate: evidence from [3H]flunitrazepam autoradiography. 228 39

Microdialysis in the human brain has been performed for the first time during thalamotomy intended to relieve tremor in patients with Parkinson's disease. The aim was to test the reliability of the microdialysis technique for biochemical characterization of a target area in the human brain during a routine operation. Microdialysis probes were introduced through the same trajectory as the lesioning electrode thus causing no additional damage to the brain. Dopamine, DOPAC, HVA, 5-HIAA, hypoxanthine, inosine, guanosine, adenosine, GABA, taurine, aspartate and glutamate were measured in the perfusate from the target region - the Vim nucleus. The results show initial high levels that reach baseline levels after 10-20 minutes. Surprisingly, consistent and reproducible levels were found, the only exception being one patient on 1-DOPA therapy who had elevated DA and metabolite levels.
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PMID:Microdialysis in the human brain: extracellular measurements in the thalamus of parkinsonian patients. 230 73


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