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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Valproic acid is a new antiepileptic drug. It has a marked effect on generalized spike-wave discharges. The exact mechanism of action is uncertain; however, some evidence suggests an effect on the metabolism of gamma-aminobutyric acid. It is rapidly absorbed from the gastrointestinal (GI) tract. Concurrent administration with phenobarbital may result in elevated phenobarbital plasma concentrations. Administration with phenytoin sodium may transiently result in lower total phenytoin plasma levels. Side effects are generally mild and include fatigue, GI disturbances, weight gain, a fine postural and resting tremor, mild thrombocytopenia, and an increase in hepatic enzymes. Platelet counts and liver function monitoring should be done during valproic acid therapy. Drowsiness may be seen in patients receiving other antiepileptic drugs concurrently.
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PMID:Valproic acid. Review of a new antiepileptic drug. 11 Feb 94

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

Tremor rats begin to exhibit clinical or electrical absence-like seizures after 6 weeks of age, and by 14 weeks of age, all have seizures. Central-type benzodiazepine receptor binding was investigated in tremor rats and control rats, aged 4 weeks and 16 weeks. Significantly lower benzodiazepine receptor density and no differences in affinity were found in the hippocampus of the tremor rats in comparison with that of control rats at both ages. This abnormality is considered to be due to a tremor gene and may be the cause of absence-like seizures in tremor rats. A significantly lower receptor density was found in the cerebellum at 4 weeks of age in the tremor rats than in the control rats. These changes may be related to tremorous movements in the tremor rats. Receptor density was significantly lower in the brainstems of tremor rats and control rats at 16 weeks of age than at 4 weeks of age, and the decrease was more marked in control rats. These facts may reflect a reduced decrease in the response to the dysfunction of gamma-aminobutyric acidergic neurons, or the function of the gamma-aminobutyric acid/benzodiazepine receptor system may be secondarily increased to suppress seizures in 16-week-old tremor rats.
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PMID:Alterations of benzodiazepine receptor binding in tremor rats with absence-like seizures. 131 79

A mutant strain of Han-Wistar rat carries an autosomal recessive gene producing spastic paresis which is characterized by ataxia, tremor and hind limb rigidity. Brains of affected rats and unaffected littermate controls were transected at the mesencephalon into rostral and caudal portions (the caudal portion contained the cerebellum and brainstem). Poly(A)+ mRNA was isolated from pooled rostral or caudal portions and injected into Xenopus oocytes. The oocytes were voltage-clamped and exposed to 1 mM L-glutamate, 500 microM kainate, 500 microM quisqualate, 200 microM N-methyl-D-aspartate (NMDA) or 1 mM gamma-aminobutyric acid (GABA). Oocytes injected with mRNA isolated from the caudal portions of the affected rat brains exhibited statistically significant increases in glutamate and kainate peak current responses compared to oocytes injected with mRNA from other brain samples. No differences were noted in the responses of the groups when exposed to quisqualate, NMDA or GABA. Cerebellar and brain stem mRNA were also isolated separately in different groups of mutants and unaffected littermates. Only oocytes injected with cerebellar mRNA from mutants displayed statistically significant increases in responses to glutamate and kainate. In parallel morphological studies changes in the cerebellum of mutants were also observed. These consisted of a loss of Purkinje cells and an asymmetrical disarrangement of the granule cell layer of cerebellar cortex. Taken together, the physiological and morphological results suggest that alterations in glutamate/kainate receptors in the cerebellum are phenotypic manifestations of the Han-Wistar mutation. The results are consistent with the hypothesis that this mutant rat might serve as a model of glutamate/kainate excitotoxicity in the brain.
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PMID:Altered excitatory amino acid function and morphology of the cerebellum of the spastic Han-Wistar rat. 168 5

omega-Conotoxin (omega-ctx) was used as a probe for studying the putative role of brain L/N-type Ca2+ channels in regulation of autonomic functions. Rats were injected intracerebroventricularly (icv) with omega-ctx, and hemodynamic, biochemical and behavioral variables were monitored. omega-Ctx (0.032-10 nmol/kg) caused a persistent, dose-dependent shaking behavior, complex thermoregulatory changes, and motor deficits lasting up to 48 h. Cardiovascular responses to omega-ctx included tachycardia (+71 +/- 16%, P less than 0.01) and elevated arterial blood pressure (+16 +/- 1%, P less than 0.05) associated with increased circulating levels of norepinephrine and epinephrine. Higher doses, 1 or 10 nmol/kg, resulted in circulatory shock and death. Central administration of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), diltiazem (100 or 1,000 nmol/kg), neomycin (100 nmol/kg, each), nifedipine (10 nmol/kg), and CdCl2 (100 nmol/kg), which represent intracellular, non-specific N-, L-, and L/N-type Ca2(+)-channel blockers, respectively, did not cause any behavioral or hemodynamic effects, whereas the L-channel agonist BAY K 8644 (100 nmol/kg icv) caused a mild transient pressor response. Pretreatment with the gamma-aminobutyric acid (GABA) agonist muscimol (icv) or a combined intravenous pretreatment with propranolol and N-methylatropine blocked the omega-ctx effects. Our data suggest that omega-ctx actions in the brain involve central GABAergic mechanisms modulated by yet a different type of Ca2+ channels not characterized by any of the known voltage-operated Ca2+ channels.
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PMID:Integrated autonomic and behavioral responses to L/N Ca2(+)-channel blocker omega-conotoxin in conscious rats. 169 39

Barbiturates retain an important place in clinical neurological practice. They are used as both diagnostic and therapeutic drugs, their most common uses being as anticonvulsant and anaesthetic agents. This article explores the current theories explaining the mechanism of action of the barbiturates, with special emphasis on their anaesthetic and anticonvulsant effects. The primary mechanism of action of barbiturates is to increase inhibition through the gamma-aminobutyric acid (GABA) system. Anaesthetic barbiturates also decrease excitation via a decrease in calcium conductance. Phenobarbital (phenobarbitone), the primary anticonvulsant barbiturate, is effective for partial, complex partial and secondarily generalised seizures. While no longer the drug of choice for all these seizure types, it remains an important and useful agent. Mysoline has been shown to be useful in the treatment of essential tremor and several other movement disorders, and as an anticonvulsant. Barbiturates are also used for their sedative-hypnotic properties. A relatively new use is in the evaluation of patients with medically intractable seizure disorders for possible surgical therapy. The roles of methohexital and amobarbital (amylobarbitone) are discussed in the section on barbiturates used as diagnostic agents. The experimental use of barbiturates is also commented on; the most important of these is perhaps the use of barbiturates in cerebral resuscitation.
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PMID:The clinical use of barbiturates in neurological disorders. 172 Mar 79

Tremorgenic mycotoxins are fungal secondary metabolites with a specific effect on the central nervous system (CNS). Except for a few toxins that are produced by Claviceps paspali, a plant parasitic fungus, most tremorgenic mycotoxins are synthesized by common saprophytic moulds of the genera Penicillium and Aspergillus. Since these compounds produce sustained tremor in the abscence of other neurotoxic effects, several authors have suggested that they are the causative agents of a number of naturally occurring incoordination syndromes in ruminants. The nature of the tremor produced by these compounds in laboratory animals is clinically indistinguishable from that occurring naturally. In particular, the most implicated tremorgenic mycotoxins are those that contain a single nitrogen atom in their molecules. Although individual compounds within this group are produced by unrelated fungal species, they all contain a similar biologically active chemical moiety. To date, their mechanism of action is unknown, and their role in neuropharmacology has not yet been defined. However, the presence of a GABA-like conformation within their active nucleus and the limited torsional flexibility of this moiety suggest that they are partial agonists of GABA (gamma-aminobutyric acid). A hypothetical mode of action of these toxins at the GABA receptor sites is presented and discussed.
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PMID:Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. 269 1

Male, Fischer strain 344 adult rats were given various doses (25-100 mg/kg) of p,p'-DDT by oral gavage, and levels of biogenic amines, their metabolites, and amino acid neurotransmitters, tremor activity, and rectal temperature were measured at several intervals (2, 5, 12, and 24 h) after dosing. Dose-related increases in rectal temperature and in tremor activity were observed at 50-100 mg/kg 12 h after dosing. Tremorigenic doses of DDT increased the 5-hydroxyindoleacetic acid (5-HIAA) level in hypothalamus, brainstem, and striatum, whereas doses of 75 and 100 mg/kg increased the 3-methoxy-4-hydroxyphenylglycol (MHPG) level in hypothalamus and brainstem and the 3,4-dihydroxyphenylacetic acid level in striatum. Six amino acids were assayed in the brainstem, hypothalamus, and striatum; aspartate and glutamate levels were increased only in brainstem at 25-100 mg/kg. No consistent changes in concentrations of taurine, glutamine, glycine, or gamma-aminobutyric acid were observed in any of the regions assayed. Time-related increases in rectal temperature were seen 2-12 h after dosing, and the presence of tremor was observed 5-12 h after dosing; for both the time of peak effect was at 12 h. The DDT-induced hyperthermia and tremor were associated with dose- and time-related increases in levels of 5-HIAA, MHPG, aspartate, and glutamate. It is suggested that an increase in the turnover rate of 5-hydroxytryptamine (5-HT) may be responsible for the DDT-induced hyperthermia, whereas increases in the metabolism of 5-HT and norepinephrine may be involved in the tremor.
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PMID:Effects of p,p'-DDT on the rat brain concentrations of biogenic amine and amino acid neurotransmitters and their association with p,p'-DDT-induced tremor and hyperthermia. 286 92

Concentrations of putative neuroactive substances glutamate, aspartate, gamma-aminobutyric acid, glycine, proline and ethanolamine were determined in ventricular cerebrospinal fluid collected in patients suffering from Parkinson's disease, pain syndromes or cerebellar tremor. Values are similar to those given in the literature for lumbar cerebrospinal fluid. A decrease in gamma-aminobutyric acid in Parkinson patients, as reported in lumbar cerebrospinal fluid, could not be observed. Further evidence for a rostro-caudal gradient for gamma-aminobutyric acid is supplied. New insights into pathophysiological mechanisms in any of the investigated syndromes may not be derived.
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PMID:Ventricular cerebrospinal fluid concentrations of putative amino acid transmitters in Parkinson's disease and other disorders. 289 52

Ethanol, a highly lipid-soluble compound, appears to exert its effects through interactions with the cell membrane. Cell membrane alterations indirectly affect the functioning of membrane-associated proteins, which function as channels, carriers, enzymes and receptors. For example, studies suggest that ethanol exerts an effect upon the gamma-aminobutyric acid (GABA)-benzodiazepine-chloride ionophore receptor complex, thereby accounting for the biochemical and clinical similarities between ethanol, benzodiazepines and barbiturates. The patient with acute ethanol poisoning may present with symptoms ranging from slurred speech, ataxia and incoordination to coma, potentially resulting in respiratory depression and death. At blood alcohol concentrations of greater than 250 mg% (250 mg% = 250 mg/dl = 2.5 g/L = 0.250%), the patient is usually at risk of coma. Children and alcohol-naive adults may experience severe toxicity at blood alcohol concentrations less than 100 mg%, whereas alcoholics may demonstrate significant impairment only at concentrations greater than 300 mg%. Upon presentation of a patient suspected of acute ethanol poisoning, cardiovascular and respiratory stabilisation should be assured. Thiamine (vitamin B1) and then dextrose should be administered, and the blood alcohol concentration measured. Subsequent to stabilisation, alternative aetiologies for the signs and symptoms observed should be considered. There are presently no agents available for clinical use that will reverse the acute effects of ethanol. Treatment consists of supportive care and close observation until the blood alcohol concentration decreases to a non-toxic level. In the non-dependent adult, ethanol is metabolised at the rate of approximately 15 mg%/hour. Haemodialysis may be considered in cases of a severely ill child or comatose adult. Follow-up may include referral for counselling for alcohol abuse, suicide attempts, or parental neglect (in children). The ethanol withdrawal syndrome may be observed in the ethanol-dependent patient within 8 hours of the last drink, with blood alcohol concentrations in excess of 200 mg%. Symptoms consist of tremor, nausea and vomiting, increased blood pressure and heart rate, paroxysmal sweats, depression, and anxiety. Alterations in the GABA-benzodiazepine-chloride receptor complex, noradrenergic overactivity, and hypothalamic-pituitary-adrenal axis stimulation are suggested explanations for withdrawal symptomatology.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute ethanol poisoning and the ethanol withdrawal syndrome. 304 Dec 44


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