UMLS:C0040822 - FACTA Search

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)

An understanding of the actions of Cannabis (Marijuana) has evolved from folklore to science over the previous hundred years. This progression was spurred by the discovery of an endogenous cannabinoid system consisting of two receptors and two endogenous ligands. This system appears to be intricately involved in normal physiology, specifically in the control of movement, formation of memories and appetite control. As we are developing an increased understanding of the physiological role of endocannabinoids it is becoming clear that they may be involved in the pathology of several neurological diseases. Furthermore an array of potential therapeutic targets is being determined--including specific cannabinoid agonists and antagonists as well as compounds that interrupt the synthesis, uptake or metabolism of the endocannabinoids. This article reviews the recent progress in understanding the contribution of endocannabinoids to the pathology and therapy of Huntington's disease. Parkinson's disease, schizophrenia and tremor.
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PMID:The role of cannabinoids in neurodegenerative diseases. 1138 76

This first clinical study of olanzapine in Japanese patients with schizophrenia was conducted to investigate the efficacy and safety of olanzapine. Eighty-one patients were included in the analysis set. Mean modal dose for those patients were 9.4 +/- 3.6 mg/day. For the primary efficacy measure (Final Global Improvement Rating score), 14.8% of patients had remarkable improvement, 59.3% of patients had moderate improvement or better, and 86.4% of patients had slight improvement or better. Results from the Brief Psychiatric Rating Scale showed improvement from baseline in all clusters including positive psychotic symptoms (thought disturbance) but also against negative symptoms (anergia). The most commonly reported treatment-emergent signs and symptoms with > or =10% incidence, were insomnia, weight increase, excitement, sleepiness, and anxiety. There was a low incidence of extrapyramidal treatment-emergent signs and symptoms, and events reported were tremor (6.2%), muscle rigidity (3.7%), and akathisia (2.5%). The most commonly reported treatment-emergent laboratory changes, with > or = 20% of incidence, were prolactin elevations (24.3%) followed by increases in triglycerides (20.4%). However, mean prolactin values tended to be normalized during the study. This study result suggests that olanzapine is an "atypical" antipsychotic.
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PMID:Efficacy and safety of olanzapine, an atypical antipsychotic, in patients with schizophrenia: results of an open-label multicenter study in Japan. 1144 86

There are at least two types of cannabinoid receptors, CB(1) and CB(2), both coupled to G proteins. CB(1) receptors exist primarily on central and peripheral neurons, one of their functions being to modulate neurotransmitter release. CB(2) receptors are present mainly on immune cells. Their roles are proving more difficult to establish but seem to include the modulation of cytokine release. Endogenous agonists for cannabinoid receptors (endocannabinoids) have also been discovered, the most important being arachidonoyl ethanolamide (anandamide), 2-arachidonoyl glycerol and 2-arachidonyl glyceryl ether. Other endocannabinoids and cannabinoid receptor types may also exist. Although anandamide can act through CB(1) and CB(2) receptors, it is also a vanilloid receptor agonist and some of its metabolites may possess yet other important modes of action. The discovery of the system of cannabinoid receptors and endocannabinoids that constitutes the "endocannabinoid system" has prompted the development of CB(1)- and CB(2)-selective agonists and antagonists/inverse agonists. CB(1)/CB(2) agonists are already used clinically, as anti-emetics or to stimulate appetite. Potential therapeutic uses of cannabinoid receptor agonists include the management of multiple sclerosis/spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, vasodilation that accompanies advanced cirrhosis, and cancer. Following their release onto cannabinoid receptors, endocannabinoids are removed from the extracellular space by membrane transport and then degraded by intracellular enzymic hydrolysis. Inhibitors of both these processes have been developed. Such inhibitors have therapeutic potential as animal data suggest that released endocannabinoids mediate reductions both in inflammatory pain and in the spasticity and tremor of multiple sclerosis. So too have CB(1) receptor antagonists, for example for the suppression of appetite and the management of cognitive dysfunction or schizophrenia.
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PMID:Cannabinoid receptors and their ligands. 1205 30

A 30-year-old white man with schizophrenia developed anorexia and nausea, and was admitted to hospital for confusion and delirium. He was on olanzapine, 10 days prior to admission. On admission, typical neuroleptic malignant syndrome (NMS) developed with elevated body temperature (39.7 degrees C), obtundation, tremor, rigidity, diaphoresis, fluctuating pupillary diameter, tachycardia, labile hypertension, elevated serum creatine kinase and severe hypernatremia (190 meq/l). Olanzepine was stopped few days after admission to the hospital and the NMS manifestations resolved by hospital day 12. The patient had all of the major manifestations of NMS. There was no other likely explanation for his illness. This is the first case reported in which NMS was associated with olanzapine and extremely elevated levels of serum sodium. Copyright 2001 John Wiley & Sons, Ltd.
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PMID:Neuroleptic malignant syndrome with olanzapine associated with severe hypernatremia. 1240 81

The strategy in the choice of antipsychotic agent must take into account the hepatic tolerance according to non-negligible incidence of liver disorders among psychiatric population (presence of risk factors like alcoholism, drugs of abuse intake, polymedication including potentially hepatotoxic drugs.). More than 1 000 drugs have been listed as being responsible of hepatic side effects; 16% of these agents were neuropsychiatric drugs. Antidepressive drugs (tricyclic agents or SSRI), mood stabilizing agents and neuroleptic drugs have been implicated in biological or/and clinical hepatotoxicity. For these reasons, some psychotropic agents have been withdrawn of the pharmaceutical market like alpidem or medifoxamine. Atrium*, sometimes used to correct tremor induced by neuroleptic drugs, has been withdrawn recently, as well. Isolated elevations of hepatic enzymes occur frequently with phenothiazines drugs (frequency evaluated to 20%) but also with other classes of neuroleptic agents, as well. On the contrary, clinical hepatitis have been more rarely described with neuroleptic drugs like phenothiazine agents (0,1-1%) or with haloperidol (0,002%). The definition of hepatotoxicity is based on biological parameters (elevation of alkaline phosphatase enzyme, SGPT, SGOT and GGT) or on clinical abnormalities (hepatitis, jaundice.). Clinical hepatitis could be either cytolytic or cholestatic. Clinical diagnosis and the research of its origin may include many investigations like abdominal ultrasonogram and percutaneous liver biopsy. The present article describes the cases of hepatic disorders reported with AAD (Atypical Antipsychotic Drugs), which are available in France (amisulpride, clozapine, olanzapine, risperidone). This new pharmacological class of antipsychotic drugs has showed great interest to improve negative symptoms of schizophrenia and to reduce disabling side effects like dystonia. According to the bibliographic data available, the following points and information must be clinically taken into account. Frequency of hepatic troubles: according to the bibliographic data, AAD appeared generally well tolerated in most cases. The frequency of hepatic troubles remains in general very low or rare. The cases published were observed with clozapine, olanzapine and risperidone. Nevertheless, some authors have observed higher frequency of hepatic enzymes elevation with some AAD. In an investigation comparing hepatic tolerance of clozapine (n=167) versus haloperidol (n=71), 37,3% of clozapine treated patients showed a relevant SGPT increase versus 16,6% with haloperidol. Nature of the hepatic troubles: among the clinical observations, asymptomatic biological disorders of the hepatic function are generally described but cytolytic or cholestatic hepatitis were reported, as well. Symptomatic hepatic dysfunctions were, sometimes, associated with other disorders like convulsions, pneumonia or malignant syndrome. Thus, hepatic check-up may be relevant in case of significant side-effect outcome. Delay time before the hepatic episode: hepatic injuries generally occurred within the first weeks of treatment but this delay highly varied in the literature from 1 to 8 weeks, 12 days to 5 months, 1 day to 17 months for clozapine, olanzapine and risperidone, respectively. These delay times are very similar to those observed with other psychotropic drugs. Reversibility of the hepatic troubles and rechallenge of the responsible agent: all cases were reversible after the AAD withdrawal except with one patient (39 years old) treated by clozapine (350 mg/day) who developed a fulminant and irreversible hepatitis after 8 weeks of monotherapy. In most cases, the AAD was withdrawn after the hepatic episode according to the significant risk of irreversible alteration. Nevertheless, normalization of hepatic enzymes has been described despite AAD maintenance at the same dosage or after dosage reduction. Rechallenge of clozapine after a first episode was performed for three patients, only one redeveloped a new hepatic disorder. According to different authors, special care is required if maintenance or rechallenge of the agent is indispensable after a first episode of isolated hepatic enzyme elevation (i.e resistance or intolerance to other treatments). In this case, biological and clinical supervision has to be carefully scheduled, which demands a satisfactory compliance from the patient. On the contrary, in case of clinical hepatotoxicity, rechallenge or maintenance is absolutely inadvisable. Mechanism of the hepatic troubles: precise mechanisms of the hepatotoxicity remain unclear. Contrary to phenothiazine drugs, no information is available on the respective rule of the agents and their metabolites. Hypersensitivity syndrome or eosinophilia has been reported, suggesting a possible immuno-allergic mechanism. Presence of risk factors: risk factors have been retrieved, in some observations, like high daily dosage, high plasmatic concentration, age, alcoholism, obesity or antecedent of hepatic disorders like Gilbert syndrome. Special care is advisable with these patients. As hepatotoxicity has been observed after surdosage (or suicide attempt), a hepatic check-up has to be performed in these clinical situations. Co-medication with hepatotoxic drugs may increase the risk as it has been suggested. In many observations, co-medication made difficult the incrimination of the AAD in the hepatic disorders outcome. Monotherapy has the great advantage to make easier the withdrawal of the responsible agent and its substitution. As drugs of abuse like cocaine or ecstasy are notoriously responsible of hepatotoxicity, they represent a probable factor of risk. Moreover, their detection is fundamental during the clinical investigation. Conclusion - Diagnosis of toxic hepatitis is mainly based on the chronology between agent introduction and hepatic disorder onset but other causes must be excluded. Bibliographic data analysis greatly contributes to confirm toxic hepatitis diagnosis. Nevertheless, this article emphasized the limits of bibliographic review to compare drugs towards tolerance. Most of the bibliographic data were case-reports for which it was sometimes difficult to provide absolute evidence of the responsibility of the agent. Moreover, spontaneous notification to health national administration is rarely systematic, in particular with isolated elevation of hepatic enzymes, and even more rarely published in international reviews. Nevertheless, according to the present data available in the literature, systematic and regular hepatic survey does not seem necessary in absence of risk factors. As for other side effects, which may occur more or less rapidly, great advantages may be obtained from psycho-education programs associating the patients in order to detect the first symptoms. Because little long-term hepatic follow-up comparing AAD is available, controlled studies should be carried out to precise the frequency and the risk factors (covariables) to prevent hepatitis outcome.
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PMID:[Hepatic tolerance of atypical antipsychotic drugs]. 1250 67

The meaning and relevance of the increased rates of neuromotoric deviation (ND) observed in patients with schizophrenia and their biological relatives remain unclear. ND could represent free-floating, independent characteristics of individuals in these families vs. signs of an increased risk for current or future mental disorder. The co-temporaneous relationship between ND and mental disorder at 6 years of age was investigated among 31 children with an increased risk for schizophrenia and similar psychoses, defined as having a mother with a history of schizophrenia or unspecified functional psychosis. As compared with high-risk cases with a low level of ND, the subgroup of 10 high-risk offspring showing notably increased rates of ND had significantly more frequent psychiatric diagnoses (typically language disorders and enuresis), poor functioning on global assessment, poor interpersonal competency and high anxiety proneness. Neuromotoric items representing "overflow" (e.g., choreatic movements, tremor) were significantly positively related to each of these mental characteristics. Among high-risk offspring, an increased rate of ND is very clearly associated with increased rates of current mental disorder, and might potentially identify a subgroup with an especially high risk for serious mental disorder in the future.
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PMID:Mental correlates of neuromotoric deviation in 6-year-olds at heightened risk for schizophrenia. 1259 85

Perospirone is a novel serotonin-2 and dopamine-2 receptor antagonist (SDA) developed in Japan. Premarketing trials suggested that this agent was effective in reducing positive and negative symptoms of schizophrenia and had a favorable side-effect profile. However, these trials included only a few elderly patients, so the usefulness of perospirone in this population remains unknown. In this report we describe the treatment of 2 elderly patients with schizophrenia for whom perospirone therapy was efficacious. Case 1 was a patient with acute exacerbation of schizophrenic symptoms after discontinuance of medication. He was treated with 12 mg of perospirone daily and his symptoms reduced markedly from the 4th day of perospirone therapy. Efficacy was assessed by the positive and negative symptom scale (PANSS); all subscales of PANSS (positive symptom, negative symptom, and general psychopathology) reduced and the total score reduced from 78 to 38 by the end of the 6th week of treatment. No side effects such as extrapyramidal symptoms were noted. Thus, perospirone may be a useful antipsychotic for elderly patients with acute schizophrenia. Case 2 was a patient who had severe negative symptoms and extrapyramidal symptoms such as tardive dyskinesia, tardive dystonia, and sialorrhea. She had been hospitalized for more than 7 years. In this patient 12 mg of perospirone was administered daily after 3 mg of risperidone had been tapered off. The negative symptom subscale and general psychopathology subscale in PANSS were gradually reduced after perospirone therapy was started. Extrapyramidal symptoms were assessed by the drug-induced extrapyramidal symptoms scale (DIEPSS), which consists of eight individual parameters and one global assessment, and each parameter is graded on a 5-point (0 = none to 4 = severe) scale. Sialorrhea, muscle rigidity, tremor, dystonia and overall sererity were improved more than 2 points by the end of the 6th week. The clinical course of this patient suggests that the clinical characteristics of perospirone and risperidone may be different, even though these agents are categorized into the same class of antipsychotics, SDA. Because this is a case report, evaluations are limited the clinical properties of perospirone. Further examination is necessary to evaluate the efficacy and safety of perospirone for elderly patients with schizophrenia, who are more vulnerable to the side effect of antipsychotics than the younger population.
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PMID:[Perospirone therapy in elderly patients with schizophrenia]. 1467 81

Clozapine is the gold standard treatment for Parkinson's disease (PD) psychosis based on double blinded, placebo controlled trials, and has also been shown to alleviate tremor and dyskinesia. There is accumulating data suggesting that clozapine may be associated with increased frequency of diabetes mellitus (DM) compared to conventional neuroleptic drugs in treating schizophrenia. Forty-four predominantly geriatric parkinsonian subjects on clozapine for psychosis, tremor or dyskinesia, on an average dose of 50.6 mg/d for a mean duration of 41 months were reviewed. The prevalence of DM in this cohort was 18.1% (8/44). This rate was similar to that reported in the aged-matched general population (prevalence = 19.3% for ages > or = 60 years). In this small study, parkinsonian patients on long-term, low dose clozapine were not at increased risk for developing DM. Larger controlled prospective studies are needed to confirm this.
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PMID:Diabetes mellitus among parkinsonian patients treated chronically with clozapine. 1546 3

Excitotoxic neonatal ventral hippocampal (NVH) lesion in rats is considered as a putative animal model of schizophrenia as lesioned animals show characteristic post-pubertal emergence of neurochemical and behavioral abnormalities analogous to some of those seen in this disease. Converging evidence points to the involvement of central cholinergic system in this neuropsychiatric disorder, and our previous studies have suggested that cholinergic neurotransmission may be altered in post-pubertal NVH lesioned rats. We investigated here muscarinic receptor reactivity in NVH lesioned animals by measuring the effects of the muscarinic receptor agonist oxotremorine on physiological responses known to be modulated by these receptors such as body temperature, salivation, tremor, pain, and prepulse inhibition of the acoustic startle (PPI). Quantitative receptor autoradiography revealed that post-pubertal NVH lesioned animals display increased levels of [3H]pirenzepine/M1-like and [3H]AFDX-384/M2-like receptor binding sites in the striatum, nucleus accumbens, and in subareas of the dorsal hippocampus. Moreover, in response to the systemic administration of oxotremorine (0.25 mg/kg), post-pubertal NVH lesioned rats exhibited increases in salivation and tremor, and a greater reduction in body temperature compared to sham control animals. Increases in the hot-plate latency were also observed suggesting enhanced antinociceptive effects of oxotremorine in post-pubertal NVH lesioned animals. Finally, oxotremorine (0.1 and 0.25 mg/kg) disrupted PPI in post-pubertal sham control rats while the muscarinic receptor antagonist biperiden (0.5 and 1.0 mg/kg) normalized this behavior in NVH lesioned rats. Taken together, these findings reveal that post-pubertal NVH lesioned rats display enhanced muscarinic receptor responsiveness, which may relate to some behavioral abnormalities reported in this animal model.
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PMID:Alterations in behavioral responses to a cholinergic agonist in post-pubertal rats with neonatal ventral hippocampal lesions: relationship to changes in muscarinic receptor levels. 1563 38

Studies of spontaneous extrapyramidal symptoms, dyskinesia and parkinsonism, in unmedicated schizophrenia are of importance in understanding their underlying pathology and relation to the psychosis. This is a study of extrapyramidal symptoms using Abnormal Involuntary Movements Scale for dyskinesia and Simpson-Angus Scale for parkinsonism in 143 schizophrenia patients who never received antipsychotic medication. Psychopathology was measured using the Positive and Negative Syndrome Scale. Dyskinesia was present in 35% of patients and parkinsonism in 15%. The two disorders coexisted in 11 subjects. Orofacial dyskinesia, rigidity and tremor were common symptoms noted. There was no significant change in the rates and total scores of dyskinesia and parkinsonism with gender, age, duration of illness or age at onset of psychosis. Dyskinesia was unrelated to psychopathology. Parkinsonism score correlated positively with the motor symptom cluster of psychopathology. Dyskinesia and parkinsonism scores correlated positively with each other and parkinsonism score discriminated presence of dyskinesia. The associations between the spontaneous abnormal movements and other aspects of schizophrenia differed from those described in treated patients. Dyskinesia and parkinsonism are an integral part of the schizophrenia disease process whose relationship with other factors could be influenced by antipsychotic drug treatment.
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PMID:Extrapyramidal symptoms in unmedicated schizophrenia. 1572 24

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