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)

Valproate has rapidly advanced as an antiepileptic drug in the last 15 years. This simple branched-chain fatty acid is strikingly different from previous antiepileptic drugs. Numerous clinical studies have found valproate to be highly effective in controlling generalized seizures, particularly as monotherapy. Ideally, valproate is given in three to four doses per day, because the elimination half-life varies from 6 to 15 hours, depending on concomitantly administered drugs and metabolic variations. Increasing the dosage raises the peak serum level and also increases the duration of time during which a minimum effective serum concentration is obtained. Drug interactions occur when valproate is administered with other drugs, especially other antiepileptic drugs. Side effects attributed to valproate include tremor, weight gain, hair loss, hair growth, hepatotoxicity, and neural tube defects in offspring of mothers. Monitoring serum valproate concentrations and seizure frequency are essential aspects of patient follow-up.
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PMID:The scope and use of valproate in epilepsy. 249 54

Mice fed chronically (3 to 4 weeks) a liquid diet containing chlordiazepoxide (CDP) became physically dependent on the drug as demonstrated by the occurrence of withdrawal signs precipitated by injection of the benzodiazepine antagonist Ro15-1788 (5 to 25 mg/kg) or by omitting CDP from the diet (spontaneous withdrawal). Very low blood concentrations of CDP, but medium to high levels of the active metabolites N-desmethyl CDP and demoxepam were found during the period of CDP administration. The Ro15-1788-induced withdrawal signs appeared within 1 min after the injection of the antagonist and lasted for at least 10 min. Quantifiable withdrawal signs included tail lift, tremor, impaired movement and handling-induced seizures. Mice undergoing spontaneous withdrawal had milder withdrawal signs such as weight loss, in appetite and suppression of runway and head-dipping activities on day 1 or day 2 of withdrawal. These signs were also present in Ro15-1788-induced withdrawal. A long-lasting rebound increase in runway and head-dipping activities occurred several days after CDP withdrawal.
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PMID:A liquid diet model of chlordiazepoxide dependence in mice. 251 28

The high pressure neurological syndrome (HPNS) occurs when man or animals are exposed to hyperbaric pressure. Four non-competitive N-methyl-D-aspartate (NMDA) antagonists - MK-801, phencyclidine (PCP), SKF 10,047 and ketamine were tested in rats for effects on the HPNS. All drugs were injected i.p. prior to compression; ketamine was also infused i.v. Control rats received saline. Rats were exposed individually to increasing helium pressure (PO2 0.5 atmospheres absolute ATA). Three endpoints were used to assess HPNS: onset pressures for tremor, myoclonus and convulsions. Neither MK-801 (0.03 and 0.3 mg/kg) nor SKF 10,047 (50 mg/kg) had any effect on the onset pressures for tremor, myoclonus or convulsions, although the type of seizure was modified from the clonic/tonic seizure seen in controls to purely clonic. PCP (5 mg/kg) had no effect on the endpoints, but pressure enhanced the excitation and stereotypy seen at 1 ATA. Ketamine (100 mg/kg i.p.) did not affect tremor or myoclonus; ketamine infused i.v. at pressure only prevented tremor and myoclonus at 'anaesthetizing' concentrations. Our results show that these non-competitive NMDA antagonists had little effect on HPNS, in contrast to competitive NMDA antagonists, such as AP7, which are highly effective. Possible explanations for this lack of effect include (1) interactions with NMDA receptor channels are pressure dependent; (2) other actions of these antagonists override their effects on the NMDA receptor channel.
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PMID:The effects of non-competitive NMDA receptor antagonists on rats exposed to hyperbaric pressure. 254 78

The effect of the focal injection of N-methyl-D-aspartate (NMDA) and 2-amino-7-phosphonoheptanoate (APH) into the substantia nigra pars reticulata (SNR) and entopeduncular nucleus (EP) on behavioural signs of the high pressure neurological syndrome (HPNS) in rats was studied. Doses of 1, 5 and 10 nmoles of NMDA or APH were injected into the SNR or EP, 10-30 min prior to the exposure of animals to a high pressure. Injection of NMDA into either SNR or EP results in a lowering of the threshold pressure for tremor by about 30%. Injection of NMDA into the SNR has no significant effect on clonic seizures whereas its injection into the EP results in a decrease of threshold pressure for clonic seizures. NMDA also facilitates the occurrence of forelimb clonus when injected into the EP. Injection of the NMDA antagonist, APH, into the SNR or EP significantly increases the threshold pressure of tremor (32.8 and 48.2% respectively). Seizure threshold is also increased by the injection of APH into either area, but nigral injections (especially the higher doses) are more protective against seizures than the EP injections. Comparing the two sites blockade of NMDA receptors within the EP is more protective against tremor, whereas in the SNR NMDA blockade is more protective against seizures.
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PMID:Studies on the role of the NMDA receptor in the substantia nigra pars reticulata and entopeduncular nucleus in the development of the high pressure neurological syndrome in rats. 255 89

Binding studies using the enantiomers of the synthetic cannabinoid 7-hydroxy-delta 6-tetrahydrocannabinol 1,1-dimethylheptyl homolog in preparations of rat brain cortical membranes reveal that the (+)-(3S,4S) enantiomer HU-211 blocks N-methyl-D-aspartate (NMDA) receptors in a stereospecific manner and that the interaction occurs at binding sites distinct from those of other noncompetitive NMDA antagonists or of glutamate and glycine. Moreover, HU-211 induces stereotype and locomotor hyperactivity in mice and tachycardia in rat, effects typically caused by NMDA receptor antagonists. HU-211 is also a potent blocker of NMDA-induced tremor, seizures, and lethality in mice. This compound may therefore prove useful as a nonpsychoactive drug that protects against NMDA-receptor-mediated neurotoxicity.
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PMID:Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker. 255 19

Among a series of 44 transgenic families established after microinjection into fertilized eggs of a plasmid DNA where the structural gene for the large T antigen of polyoma virus is located downstream from the viral early promoter-enhancer region, one family with a hereditary neurological disorder was observed. At about three weeks of age, these animals developed a syndrome of constant tremor with recurrent seizures. Histological and ultra-structural examination revealed extensive dysmyelination in the white matter of the brain stem, cerebellum and spinal cord, as well as of peripheral nerves. This phenotype is reminiscent of that of the mouse "twitcher" (twi) mutant and of the human hereditary leukodystrophies. Expression of the viral sequences, assayed by Northern analysis and immunolabeling of T antigen, occurred predominantly in cells of the central nervous system. Integration of the transgene was mapped by in situ hybridization on metaphasic plaques in region B-C1 of chromosome 12 (where the twi locus was previously localized). Long-term cultures of cells with neural characteristics could be established readily from the brain of the transgenic mice.
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PMID:Neurological disorder in transgenic mice that express the large T antigen of polyoma virus in the nervous system. 256 75

1. The effects of the benzodiazepine receptor antagonists Ro 15-1788 (flumazenil) and the beta-carboline ZK 93426 were compared in dogs before and after chronic treatment with diazepam. 2. In diazepam-naive dogs, the most prominent behavioural alterations occurring during or after i.v. infusion of Ro 15-1788 up to a dose of 20 mg kg-1 were transient sedation, ataxia, and 'hot foot' behaviour, whereas behavioural alterations observed after ZK 93426 were not different from those observed after i.v. infusion of vehicle alone. This indicates that, in contrast to Ro 15-1788, ZK 93426 did not exert partial agonistic activity at benzodiazepine receptors. 3. In dogs treated 3 times daily with diazepam, 1 mg kg -1 orally, for 1 week, both benzodiazepine antagonists precipitated abstinence symptoms but the number and severity of withdrawal signs induced by Ro 15-1788 were greater than with ZK 93426. 4. In dogs treated 3 times daily with diazepam, 2 mg kg-1 orally, for 2 weeks, severe abstinence symptoms were precipitated in all animals by infusion of either antagonist but differences were found in the type of the symptoms: Ro 15-1788 induced rigid postures or rigid walking with increased muscle tone, tremor, twitches and jerks, whereas ZK 93426 did not alter motility but induced generalized myoclonic jerks and tonic-clonic seizures. A generalized tonic-clonic seizure was also observed in one dog of the trial with infusion of Ro 15-1788. 5. Plasma level determinations during chronic treatment diazepam showed marked accumulation of the major active metabolite desmethyldiazepam, whereas diazepam levels were at least 15 times lower, which might suggest that desmethyldiazepam was responsible for the development of physical dependence on diazepam.
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PMID:Physical dependence on diazepam in the dog: precipitation of different abstinence syndromes by the benzodiazepine receptor antagonists Ro 15-1788 and ZK 93426. 256 47

Movement disorders are well-known presenting signs of metabolic disorders. Focal motor abnormalities may be the chief initial presentation of diabetes mellitus in the nonketotic hyperglycemic state in 6% of patients. Nonketotic hyperglycemia (NKH), in particular, may manifest any of a wide variety of movement disorders. These have been described as focal seizures, epilepsia partialis continua, myoclonus, and opsoclonia. There are descriptions of movement disorders in hyperglycemia that are similar to the coarse flapping tremor of asterixis, the posturing of paroxysmal kinetogenic choreoathetosis, and of "fencing (stance) seizures." Disorders of facial motor function including aphasia, facial muscle twitching and jerking, and disorders of muscular tone have been described. These may include hemiparesis and hemiplegias as well as increased tone, in some cases mimicking the nuchal rigidity of meningitis. The movement disorders in NKH may mimic cerebral vascular accidents, meningitis, or psychiatric disorders, as well as various types of seizures. Clinicians may be able to avoid expensive and time-consuming diagnostic evaluations to rule out NKH in patients with movement disorders. We present two patients with focal motor abnormalities associated with nonketonic hyperglycemia and review the pertinent literature.
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PMID:Movement disorders as a manifestation of nonketotic hyperglycemia. 260 Mar 93

We report the clinical and neuropathological manifestations of Alzheimer's disease (AD) in nine kindreds of German ancestry all originating from the same two adjacent villages on the West bank of the Volga River. There have been 89 known demented persons (53 male, 36 female). Mean age of onset is 57.6 +/- 8.4 years with a range of 40 to 84. Mean age at death is 66.5 +/- 7.6 years with a range of 50 to 80. Mean disease duration is 10.3 +/- 4.8 years with a range of 3 to 23. Detailed medical records were available on 50 individuals. Of these, 24% had a seizure, 72% language disturbance, 36% rigidity, 16% tremor and 12% myoclonus. There were 15 autopsies on demented persons from 6 of the kindreds. One brain suggested Creutzfeldt-Jakob disease (CJD) in a woman with the typical clinical course. The remaining 14 brains showed typical neuropathological characteristics of AD including neuritic amyloid plaques, neurofibrillary tangles, amyloid angiopathy and granulovacuolar change. Amyloid plaques were also seen in the cerebellum in all but one brain in which this region was available for review. Autopsy material from five brains in four families has been stained with antibody directed against the amyloid peptide; in all cases, the neuritic plaques stained positively. Many of the families share common surnames. It is likely that these Volga German kindreds carry the same genetic mutation leading to Alzheimer's disease; and thus, they are a valuable resource for genetic investigations of AD. Thus far, the disease in these kindreds does not show close linkage to either the D21S1 or beta amyloid gene loci on chromosome 21.
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PMID:Characteristics of familial Alzheimer's disease in nine kindreds of Volga German ancestry. 260 19

High-dose treatment with pilocarpine hydrochloride, a cholinergic muscarinic agonist, induces seizures in rodents following systemic or intracerebral administration. Pilocarpine seizures are characterized by a sequential development of behavioral patterns and electrographic activity. Hypoactivity, tremor, scratching, head bobbing, and myoclonic movements of the limbs progress to recurrent myoclonic convulsions with rearing, salivation, and falling, and status epilepticus. The sustained convulsions induced by pilocarpine are followed by widespread damage to the forebrain. The amygdala, thalamus, olfactory cortex, hippocampus, neocortex, and substantia nigra are the most sensitive regions to epilepsy-related damage following convulsions produced by pilocarpine. Spontaneous seizures are observed in the long-term period following the administration of convulsant doses of pilocarpine. Developmental studies show age-dependent differences in the response of rats to pilocarpine. Seizures are first noted in 7-12 day-old rats, and the adult pattern of behavioral and electroencephalographic sequelae of pilocarpine is seen in 15-21-day-old rats. During the third week of life the rats show an increased susceptibility to the convulsant action of pilocarpine relative to older and younger animals. The developmental progress of the convulsive response to pilocarpine does not correlate with evolution of the brain damage. The adult pattern of the damage is seen after a delay of 1-2 weeks in comparison with the evolution of seizures and status epilepticus. The susceptibility to seizures induced by pilocarpine increases in rats aged over 4 months. The basal ganglia curtail the generation and spread of seizures induced by pilocarpine. The caudate putamen, the substantia nigra, and the entopeduncular nucleus govern the propagation of pilocarpine-induced seizures. The antiepileptic drugs diazepam, clonazepam, phenobarbital, valproate, and trimethadione protect against pilocarpine-induced convulsions, while diphenylhydantoin and carbamazepine are ineffective. Ethosuximide and acetazolamide increase the susceptibility to convulsant action of pilocarpine. Lithium, morphine, and aminophylline also increase the susceptibility of rats to pilocarpine seizures. The pilocarpine seizure model may be of value in designing new therapeutic approaches to epilepsy.
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PMID:Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. 264 33


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