Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To clarify clinical roles of sigma receptor binding affinity of neuroleptics, neck dystonia induced by microinjection of sigma receptor ligands and neuroleptics into rat red nucleus was investigated. DTG and (+)-3-PPP, putative sigma receptor agonists, induced neck dystonia in dose-dependent and reversible manner. Haloperidol and perphenazine induced dystonia in the same way as sigma receptor agonists, whereas zotepine and (-)-sulpiride did not. The rank order of potency in induction of dystonia and sigma receptor affinity of these compounds showed positive correlation. Although BMY-14802 has a high affinity for sigma receptors, it never produced dystonia by itself. On the other hand, combined injection of BMY-14802 with DTG attenuated DTG-induced dystonia. Therefore, it is suggested that typical neuroleptics such as haloperidol act agonistic and atypical neuroleptics such as BMY-14802 act antagonistic at rubral sigma receptors in the induction of neck dystonia.
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PMID:BMY-14802 reversed the sigma receptor agonist-induced neck dystonia in rats. 901 2

Neuroleptics induce several extra-pyramidal side effects, such as akathisia, acute dystonia and parkinsonism. Although recently developed atypical neuroleptics ameliorate some of these side effects, akathisia remains a common and severely distressing adverse reaction. Several drugs are reported to be of clinical use for the pharmacological treatment of akathisia. In particular, the beta-adrenoceptor blocker, propranolol, has been widely used for the treatment of akathisia, but it does not ameliorate other extra-pyramidal side effects. To identify the neural substrates of akathisia, we investigated the effects of propranolol on haloperidol-induced Fos expression in rat brain. Haloperidol (1 mg/kg) induced Fos-positive nuclei in several regions of the brain, including the cingulate cortex area 3, piriform cortex nucleus accumbens, caudate-putamen, ventral lateral septum and parietal cortex. Pretreatment with propranolol (5 mg/kg) reduced the number of Fos-positive nuclei in the cingulate cortex area 3, the piriform cortex and area 1 of the parietal cortex. Injection of vehicle by itself tended to increase Fos expression in the cingulate cortex area 3 and the piriform cortex. Considering the functions of these brain regions, we speculate that the most plausible neural framework for haloperidol-induced akathisia involves area I of the parietal cortex, but possible roles for the cingulate cortex area 3 and the piriform cortex cannot be ruled out.
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PMID:Propranolol attenuates haloperidol-induced Fos expression in discrete regions of rat brain: possible brain regions responsible for akathisia. 974 42

The primary objective of this study was to compare the objective and subjective effects of amisulpride with those of a classic antipsychotic, haloperidol, when both were given to healthy volunteers in representative therapeutic doses over 5 days. The secondary objective was to compare the effects of relatively low and high doses of amisulpride to confirm the suspected duality of its pharmacologic activity. Twenty-one subjects participated in the four-way, randomized, double-blind, crossover study with repeated daily doses of amisulpride 50 mg, amisulpride 400 mg, haloperidol 4 mg, and placebo. Subjects were institutionalized during treatment periods and were under 24-hour medical supervision. They underwent a series of psychomotor and cognitive tests 1 hour before and 3 and 6 hours after dosing on days 1 and 5. Their extrapyramidal disturbances and drug-related feelings were assessed at the end of each replication. Psychiatric interviews and ratings of depression, subjective well-being, and negative symptoms occurred on day 4. Amisulpride 50 mg had no significant effect on any parameter. Amisulpride 400 mg had several adverse effects on psychomotor and, although less severe, on cognitive performance on the fifth day only. Amisulpride 400 mg produced no significant extrapyramidal disturbances in the group as a whole, although it may have in some individual subjects. Also, it produced no signs of mental disturbances on clinical rating scales or during a structured psychiatric interview. Haloperidol ubiquitously impaired psychomotor and cognitive performance in a similar fashion after the first and the final doses. It produced extrapyramidal disturbances in nearly every subject, the most common being akathisia and the most severe, in the case of one individual, being acute dystonia. Unlike amisulpride, haloperidol produced a number of mental disturbances, the most noteworthy being negative symptoms. Amisulpride seems to be a well-tolerated drug. Its side effects should be much less troublesome to patients using the drug on a long-term basis than those of classic antipsychotics, like haloperidol.
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PMID:Psychomotor, Cognitive, extrapyramidal, and affective functions of healthy volunteers during treatment with an atypical (amisulpride) and a classic (haloperidol) antipsychotic. 1035 27

We describe a case series of five patients with unusual presentations of acute dystonia seen over a 2-week period. Haloperidol, prescribed and allegedly purchased 'on the street', was thought to be a possible cause in each case. Bizarre clinical presentations and delayed onset of symptoms may make diagnosis difficult. A high index of suspicion combined with a careful drug history is essential.
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PMID:Epidemic dystonia in Cork. 1178 96

Haloperidol is a widely used neuroleptic drug for the treatment of acute and chronic psychosis. The use of haloperidol is limited by extrapyramidal movement disorders such as Parkinsonism, akathesia, dystonia, and tardive dyskinesia (TD). Treatment with haloperidol increases oxyradicals which are implicated in TD. Spirulina is widely used as nutritional supplement rich in proteins and antioxidants. The present study is proposed to study the effect of spirulina on haloperidol induced TD and oxidative stress by studying TD, various enzymatic and nonenzymatic antioxidants and lipid peroxidation. Haloperidol 1 mg/kg/i.p was used to induce vacuous chewing movements in rats. Spirulina maxima suspended in 1% between 80 at a dose of 45, 90 and 180 mg/kg were administered by gavage along with haloperidol from 21st day to 49th day of treatment. Spirulina supplementation at a dose of 180 mg/kg significantly improved enzymatic and nonenzymatic antioxidants and decreased the tardive dyskinesia induced by haloperidol. In conclusion, the results of present investigation suggest that spirulina decreases haloperidol induced oxidative stress and TD by many mechanisms as it is cocktail of antioxidants. On chronic use it may inhibit haloperidol induced reduced expression of DNA thereby increases the expression of enzymatic and nonenzymatic antioxidants and protects against oxidative stress induced neurodegeneration and TD.
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PMID:Effect of spirulina maxima on the haloperidol induced tardive dyskinesia and oxidative stress in rats. 1753 Jan 60

Reported herein is a case of methamphetamine psychosis in which tardive dystonia was treated successfully with clonazepam. The patient was a 69-year-old man who had taken methamphetamine habitually for approximately 40 years. Auditory hallucinations had developed 25 years previously, for which haloperidol had been prescribed. Tardive dystonia had developed in December 2005. Haloperidol was withdrawn and risperidone or olanzapine alone had been administered, but neither had improved the dystonic posture. However, when clonazepam was added, a gradual improvement in the dystonic posture became evident. Tardive dystonia is currently treated on a trial-and-error basis. Accumulation of further cases similar to the present one is very important for establishing an effective treatment.
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PMID:Methamphetamine psychosis in which tardive dystonia was successfully treated with clonazepam. 1808 35

Typical antipsychotics such as haloperidol exert their therapeutic effects via blockade of dopamine (DA) D(2) receptors, leading to extrapyramidal symptoms (EPS) in humans and catalepsy in rodents. In contrast, atypical antipsychotics and new generation D(2)/5-HT(1A) antipsychotics have low cataleptogenic potential. However, there has been no systematic comparative study on the effects of these different classes of antipsychotics in non-human primates, a species displaying a more sophisticated repertoire of behavioural/motor activity than rats. Once weekly, six young adult female non-haloperidol-sensitised cynomolgus monkeys were treated i.m. with a test compound and videotaped to score catalepsy-associated behaviour (CAB: static postures, unusual positions and crouching). Haloperidol, risperidone, olanzapine, nemonapride and remoxipride induced, to different extents, an increase in unusual positions (a response akin to dystonia), some crouching and static postures. In contrast, clozapine, quetiapine, ziprasidone and aripiprazole produced much lower or no unusual positions; clozapine also produced marked increases in static postures and crouching. Among novel D(2)/5-HT(1A) antipsychotics, SLV313 and F15063 augmented the number of unusual positions, albeit at doses 16-63 times higher than those of haloperidol for approximately the same score. SSR181507 and bifeprunox produced moderate static postures, little crouching and negligible unusual positions. These data provide the first comparative analysis in cynomolgus monkeys of EPS liability of conventional, atypical and novel D(2)/5-HT(1A) antipsychotics. They indicate that the latter are less prone than haloperidol to produce CAB, and provide a basis for comparison with rodent catalepsy studies.
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PMID:Differences among conventional, atypical and novel putative D(2)/5-HT(1A) antipsychotics on catalepsy-associated behaviour in cynomolgus monkeys. 1946 24

Antipsychotic drugs may cause extrapyramidal symptoms (EPS), such as dyskinesia and dystonia. These effects are believed to involve dysfunctional striatal dopamine transmission. Patients with schizophrenia show increased prevalence of cannabis abuse and this has been linked to severity of EPS. Endocannabinoids modulate striatal dopamine activity via type 1 cannabinoid (CB(1)) receptors, and studies in rats and humans suggest beneficial effects of CB(1) ligands on EPS. The present study explored the effects of CB(1) receptor ligands on oral dyskinesia induced by the dopamine D(1) receptor agonist SKF81297 (SKF) and acute dystonia induced by the dopamine D(2) receptor antagonist haloperidol in Cebus apella monkeys. The monkeys were sensitised to EPS by prior exposure to D(2) receptor antagonists. SKF (0.3 mg/kg) was administered alone and in combination with the CB(1) agonist CP55,940 (0.0025-0.01 mg/kg) or the CB(1) antagonist SR141716A (0.25-0.75 mg/kg). Haloperidol (individual doses at 0.01-0.02 mg/kg) was administered alone and in combination with CP55,940 (0.005 or 0.01 mg/kg) or SR141716A (0.5 or 0.75 mg/kg). Subsequently, the monkeys were videotaped, and the recordings were rated for oral dyskinesia or dystonia. SKF-induced oral dyskinesia was dose-dependently reduced by CP55,940, with no effect of SR141716A. Haloperidol-induced dystonia was not affected by either CP55,940 or SR141716A.
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PMID:Effects of cannabinoid CB1 receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys. 2102 43

Drug induced dystonic reactions are among common presentations of patients in emergency departments, and typically occur with antidopaminergic agents as their extra-pyramidal side effects. Dystonic reactions usually occur within the first few hours or days after commencing a drug or dose increase. Unlike other extra-pyramidal side effects, a patient may experience acute dystonic reactions (ADRs) with the administration of just a single dose. Oromandibular dystonia is a subtype of dystonia which can present with perioral manifestations. In extreme cases, it can lead to temporomandibular dislocation. Haloperidol, as a high potent typical antipsychotic drug, can induce dystonia with blocking D2 dopamine receptors. The present paper reports a case of bilateral dislocation of temporomandibular joint following ingestion of haloperidol in a suicidal attempt in a 17 years old girl.
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PMID:Bilateral dislocation of temporomandibular joint induced by haloperidol following suicide attempt: a case report. 2241 92

Extra-pyramidal symptoms (EPS) such as akinesia, dystonia, gait alteration and tremors are observed when dopamine D2-receptors are blocked by pharmacological agents such as haloperidol. These alterations produce a Parkinson disease-like state (PLS). Physical exercise has been proven to improve gait and locomotor symptoms in Parkinson's disease; we sought to elucidate the effects of physical exercise on PLS induced by chronic administration of haloperidol in rats. We used 48 rats distributed into four groups: Control, Exercise, Haloperidol, and Hal+Exe. All the animals received a daily injection of saline or haloperidol for 30 days, and the exercise groups underwent a daily 30-minute exercise protocol for 20 days. The animals were subjected to the ink-paw test, bar test and open-field test throughout the training period. The haloperidol-induced akinesia increased throughout the days of injections, but exercise was shown to alleviate it. The assessment showed shortened stride length and increased stance width with the use of haloperidol, which were significantly alleviated by exercise. These results indicate that exercise could be an interesting approach towards reducing unwanted EPS caused by haloperidol.
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PMID:Physical exercise down-regulated locomotor side effects induced by haloperidol treatment in Wistar rats. 2329 Sep 38


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