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

We have demonstrated that injection of manganese into one caudate nucleus in rats results in a predominant ipsilateral turning behavior, accompanied at higher doses by an intermittent, alternating and dose-related incidence of contralateral turning and stereotypies. Although the pharmacological evidence produced (effect of alpha-MT, L-DOPA, pargyline) indicates a definite participation of the dopaminergic system in the latter two phenomena, it is probable that ipsilateral turning is the result of involvement of other transmitter systems as well. Tegmental serotoninergic and intrastriatal cholinergic pathways appear to be involved in the production of the basic postural asymmetry resulting in turning. The amount of interference with the nigrostriatal and mesolimbic dopaminergic pathways may determine the speed of circling, and the concurrent inhibition of locomotion. This is more evident with bilateral injections. Manganese appears to act at presynaptic levels within the striatum by blocking release of the transmitter, thus creating a localized, relative deficit in caudate function. The end result is the release of the dominant "ipsilateral syndrome-inducing system' from its inhibitory control. Repeated or chronic administration of this metal in man or animals is known to result in a brain dopamine and/or serotonin deficit commensurate with the clinical manifestations of bradykinesia and dystonia. Our results are compatible with the anatomical findings of Poirier and collaborators and tend to support the dual ipsilateral and contralateral syndrome-inducing systems in the caudate postulated by Cools, and the complementary roles of dopamine, serotonin and acetylcholine within that nucleus. No one transmitter is involved alone in the experimental production of the manganese syndrome, or of its component symptoms.
 ...
PMID:Behavioral effects in rats following intrastriatal microinjection of manganese. 117 15

In an inbred line of Syrian hamsters, attacks of sustained dystonic postures of the limbs and trunk can be initiated by handling or mild environmental stimuli (e.g. new cage). The severity of the dystonic syndrome in these mutant hamsters (gene symbol dtSZ) is age-dependent, with a peak at about 30-40 days of age. A scoring system for grading the type and severity of the dystonic attacks can be used to study the activity of drugs against dystonic movements with individual pre- and post-drug vehicle trials as control. The effects of drugs which alter dopaminergic or cholinergic functions in the brain were studied in selectively bred dystonic hamsters and age-matched non-dystonic controls. The dopamine precursor levodopa (injected together with carbidopa) and the dopamine receptor agonist apomorphine increased the severity of dystonia in hamsters when administered prior to the age of maximum severity of dystonia. A very similar effect was observed with the cholinomimetic pilocarpine. In contrast, the dopamine receptor antagonist haloperidol caused a marked overall reduction in dystonic movements. Anticholinergic drugs, i.e. trihexyphenidyl and biperiden, increased the latency to onset of the dystonic attack, but did not reduce its severity. No differences were observed between dystonic and non-dystonic hamsters with respect to extent and duration of stereotypies induced by dopaminergic and cholinergic drugs or hypolocomotion and catalepsy produced by haloperidol. The data suggest that dopaminergic hyperactivity might be involved in the pathophysiology of dystonia in dtSZ mutant hamsters.
 ...
PMID:Effects of pharmacological manipulation of dopaminergic and cholinergic neurotransmission in genetically dystonic hamsters. 132 71

A patient with tardive dyskinesia dominated by pelvic thrusting movements is described. A retrospective review of the clinical features documented in patients with metoclopramide- and antipsychotic-induced tardive dyskinesias seen over a six year period demonstrated that the occurrence of pronounced pelvic thrusting and respiratory dyskinesias were significantly more common in the metoclopramide treated group. The occurrence of bucco-linguomasticatory movements, limb stereotypies or chorea, and mild truncal or abdominal rocking were not significantly different between the two groups. None of the tardive dystonia patients had metoclopramide as the causative agent. These findings will require confirmation in larger, better matched patient populations. Whether the differences relate to different pharmacologic profiles of drug action, patient populations exposed, or other factors, remains to be elucidated.
 ...
PMID:Clinical differences between metoclopramide- and antipsychotic-induced tardive dyskinesias. 197 49

Three recently arrived drug naive Cebus apella monkeys with "spontaneous" stereotyped oral movements were treated with apomorphine and haloperidol using a wide dose range. Low doses of apomorphine (0.05-0.1 mg/kg) suppressed the oral stereotypies without affecting normal behaviour such as grooming and scratching. Higher doses of apomorphine (0.25-1.0 mg/kg) and haloperidol (0.01-0.1 mg/kg) also decreased or abolished the oral stereotypies, but induced generalized stereotypies (apomorphine) or dystonia/parkinsonism (haloperidol), suppressing normal behaviour. The findings indicate that dopamine is involved in these presumably stress-induced (not drug-induced) stereotypies.
 ...
PMID:Effects of apomorphine and haloperidol on "spontaneous" stereotyped licking behaviour in the Cebus monkey. 392 90

This article focuses on the current knowledge about movement disorders associated with alcohol and drug abuse. Chronic alcohol use can produce a wide spectrum of movement disorders including tremor, withdrawal parkinsonism and dyskinesias, cerebellar ataxia, and asterixis. MPTP, a neurotoxin first reported to cause parkinsonism in a group of drug abusers, has provided important insights into the pathogenesis of Parkinson's disease. There is a growing body of literature providing evidence that dyskinesias such as tics and dystonia may be precipitated or exacerbated by cocaine. Amphetamines have been implicated in the production of stereotypies and exacerbation of tics.
 ...
PMID:Movement disorders. 837 47

To determine: (1) whether the apparent lack of efficacy of dopamine D1 (D1) antagonists in the clinic might be attributable to development of tolerance to antipsychotic effects; and (2) whether combined D1 and D2 antagonism might contribute to clozapine's clinical profile, eight Cebus apella monkeys were chronically treated with a D1 antagonist (NNC 756) ((+)-8-chloro-7-hydroxy-3-methyl-5-(7-(2,3- dihydrobenzofuranyl)-2,3,4,5-tetrahydro-1H-3-benzazepine), a D2 antagonist (raclopride) or a combination of the two antagonists. Prior neuroleptic exposure had resulted in oral dyskinesia in seven monkeys and sensitization to dystonia in all, yielding a model for acute and chronic extrapyramidal side effects (EPS). Dextroamphetamine-induced motoric unrest and stereotypies were used as a psychosis model. We found tolerance toward dystonic symptoms during D1 and D1 + D2 treatments but not during D2 treatment. D2 but not D1 or D1 + D2 antagonism caused exacerbation of dyskinesia. Both D1 and D1 + D2 antagonism were superior to D2 antagonism alone in counteracting the amphetamine-induced behaviors, with no tolerance to antiamphetamine effects. These findings suggest: (1) reasons other than tolerance (e.g., differences among antagonists) may explain the lack of efficacy in clinical trials with D1 antagonists; and (2) that D1 antagonism alone or combined and modest D1 and D2 antagonism offers the potential of antipsychotic efficacy with a lower risk of EPS than traditional D2 antagonism. Further clinical trials with D1 or combined D1 and D2 antagonists are, therefore, recommended.
 ...
PMID:Chronic dopamine D1, dopamine D2 and combined dopamine D1 and D2 antagonist treatment in Cebus apella monkeys: antiamphetamine effects and extrapyramidal side effects. 988 83

Xanomeline is a muscarinic M(1)/M(4) preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects (EPS) at therapeutically relevant doses. In the present study, we examined whether the xanomeline-induced functional dopamine antagonism found in rodent studies could also be observed in nonhuman primates. In addition, we studied whether the lack of EPS observed in rodents also applies to primates. To this end, we investigated the effects of xanomeline on the behavior induced by D-amphetamine and (-)-apomorphine in drug-naive Cebus apella monkeys. Antipsychotic compounds antagonize amphetamine-induced motor unrest and stereotypies in this species. Xanomeline inhibited D-amphetamine-induced motor unrest, stereotypies and arousal as well as apomorphine-induced stereotypies and arousal in drug-naive Cebus apella monkeys. Xanomeline did not induce EPS but vomiting occurred in some monkeys at high doses, in accordance with emetic events observed in Alzheimer patients following xanomeline administration. Even when xanomeline was tested in EPS-sensitized Cebus apella monkeys, EPS were not observed at the dose range of xanomeline used in the D-amphetamine-apomorphine combination study (0.5-3 mg/kg). However, when xanomeline was tested at 4 mg/kg, moderate dystonia was seen in two out of three monkeys. It is concluded that xanomeline inhibits D-amphetamine- and (-)-apomorphine-induced behavior in Cebus apella monkeys at doses that do not cause EPS. These data further substantiate that muscarinic receptor agonists may be useful in the pharmacological treatment of psychosis.
 ...
PMID:The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys. 1270 Jul 11

Rett syndrome is an X-linked neurodevelopmental disorder resulting in profound psychomotor retardation. It is usually diagnosed by a pediatrician or pediatric neurologist. Adult neurologists may, therefore, overlook the possibility of Rett syndrome in women with psychomotor retardation of unknown etiology. We report the case of a woman diagnosed with Rett syndrome at age 49 years. This report emphasizes the diagnostic value of movement disorders, including hand stereotypies, Parkinsonism, and dystonia, in adults with Rett syndrome.
 ...
PMID:Rett syndrome: an overlooked diagnosis in women with stereotypic hand movements, psychomotor retardation, Parkinsonism, and dystonia? 1721 43

Rett syndrome (RS) is one of the best human models to study movement disorders. Patients evolve from a hyperkinetic to a hypokinetic state, and a large series of abnormal movements may be observed along their lives such as stereotypies, tremor, chorea, myoclonus, ataxia, dystonia, and rigidity. The aim of this work was to analyze movement disorders in RS patients with a detected MECP2 mutation, as well as their correlation with genotype, in a clinically and genetically well-characterized sample of patients, and thus contribute to redefine the clinical profile of this disease. In this study, we included 60 patients with detected MECP2 mutations. These were categorized and grouped for analysis, according to (1) type of change (missense or truncating, including nonsense and frameshift but also large deletions) and (2) location of the mutation. Differences were found concerning the frequency of independent gait, dystonia, type of tremor, and global score severity when comparing the group of patients with missense and truncating mutations. We also found differences in the presence, distribution, severity, or type of movement disorders in the two groups of patients according to the median duration of the disease (less than 60 months; 60 months or more). We conclude that movement disorders seem to reflect the severity and rate of progression of Rett disorder, patients with truncating mutations presenting a higher rate and more severe dystonia and rigid-akinetic syndrome, when comparing groups with similar time of disease evolution.
 ...
PMID:Movement disorders in Rett syndrome: an analysis of 60 patients with detected MECP2 mutation and correlation with mutation type. 1851 55

Myoclonic jerks and myoclonic status (MS) are sometimes difficult to distinguish clinically from movement disorders such as hand stereotypies, tremor, and dystonia in Rett syndrome. We describe a rare and complete video-polygraphic study of a girl with Rett syndrome (MECP2 mutation) and MS misdiagnosed as movement disorders and disclosed after video-polygraphic recordings. Corresponding to closely recurring activity of diffuse spike and polyspikes-wave-type paroxysms, rhythmic and, especially, arrhythmic myoclonias, usually asymmetrical and asynchronous, involving mainly right muscle deltoid and rarely followed by an inhibitory phenomenon, appeared. The MS improved and, most importantly, disappeared after the use of levetiracetam, with an evident antimyoclonic efficacy and a marked improvement of daily life for the patient and her caregivers. The difficulty in differentiating some typical nonepileptic behavioral features and movement disorders of patients with Rett syndrome from seizures was overcome using prolonged video-polygraphic recordings in our case.
 ...
PMID:Myoclonic status misdiagnosed as movement disorders in Rett syndrome: a video-polygraphic study. 1960 60


1 2 3 4 Next >>