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)

Peak dose dyskinesia is a major problem in the treatment of parkinsonian patients with levodopa and yet this remains the best pharmacological agent for treating the condition. The hypothesis which this research set out to test was that thalamotomy in the area of the thalamus which receives the input from the medial segment of the globus pallidus would decrease or prevent the dyskinesia. A well established primate model of parkinsonism was used. Eight monkeys (Macaca fascicularis) were rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Regular dosing with levodopa or apomorphine reliably resulted in peak dose dyskinesia. Thalamotomy was carried out using a radiofrequency electrode. To ensure that the appropriate area of the thalamus was targeted, that is the area receiving the pallidal input, an anatomical tracing study was carried out. The anterograde anatomical tracer horseradish peroxidase, covalently bound to wheatgerm agglutinin, was injected into the medial segment of the globus pallidus bilaterally in three monkeys. The target site for thalamotomy was accurately worked out from the tracings obtained. Chorea was usually abolished and always reduced by a thalamotomy in the pallidal terminal territory. This result was obtained after 10 thalamotomies: 4 animals receiving bilateral lesions, with an interval between operations, and 2 animals undergoing unilateral surgery. Lesions in three control sites were carried out and had no permanent effect on chorea. The effect of lesions in other areas was also assessed. Dystonia was not relieved by any thalamic lesion. Thalamotomy is a long established procedure used to help parkinsonian tremor. Appropriately placed thalamotomy should be considered for the relief of disabling peak dose dyskinesia, which is predominantly choreic, in parkinsonian patients on otherwise successful levodopa therapy.
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PMID:The use of thalamotomy in the treatment of levodopa-induced dyskinesia. 158 Jan 97

Chediak-Higashi syndrome (CHS) is a rare autosomal-recessive disorder characterized by immune deficiency, partial oculocutaneous albinism, and large eosinophilic, peroxidase-positive inclusion bodies in granule-containing cells. The adult form of CHS manifests during late childhood to early adulthood and is marked by various neurologic sequelae, including parkinsonism, dementia, spinocerebellar degeneration, and peripheral neuropathy. We report the case of a 29-year-old man with adult CHS who exhibited a progressive asymmetric parkinsonism, including rest tremor, and axial, cervical, and appendicular dystonia. The diagnosis was confirmed by the presence of characteristic large peroxidase-positive granules within leukocytes and markedly decreased natural killer cell function. Levodopa/carbidopa and amantadine provided benefit for tremor. CHS, although rare, should be considered in the differential diagnosis of young adult parkinsonism.
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PMID:Adult Chediak-Higashi parkinsonian syndrome with dystonia. 1092 82

The extensive pharmacological evaluation of JL 13 as an atypical antipsychotic drug has revealed a close similarity to clozapine, however with some major advantages. JL 13 was characterized as a weak D(2) antagonist, both in vitro and in vivo, with a strong affinity for the D(4) and the 5-HT(2A) receptors. It has no affinity for the 5-HT(2C) receptor. In vivo microdialysis experiments in rat showed that JL 13, like clozapine, preferentially increased extracellular dopamine concentrations in the prefrontal cortex compared to nucleus accumbens or striatum. Behavioral studies showed that JL 13, like clozapine, has the profile of an atypical antipsychotic. Thus, JL 13 did not antagonize apomorphine-induced stereotypy nor did it produce catalepsy, but it antagonized apomorphine-induced climbing in rodents. It was inactive against d-amphetamine-induced stereotypy but antagonized d-amphetamine-induced hyperactivity in the mouse. Likewise, in the paw test, it was more effective in prolonging hindlimb retraction time than prolonging forelimb retraction time. Like other antipsychotic drugs, JL 13 reversed the apomorphine- and amphetamine-induced disruption of prepulse inhibition. In a complex temporal regulation schedule in the dog, JL 13 showed a high resemblance with clozapine without inducing sialorrhea, palpebral ptosis or any significant motor side effects. In rats and squirrel monkeys JL 13 induced a high degree of generalization (70%) to clozapine. Regarding behavioral toxicology, JL 13 did not produce dystonia or Parkinsonian symptoms in haloperidol-sensitized monkeys. After acute administration, again like clozapine, JL 13 induced only a transient increase in circulating prolactin. Last but not the least, regarding a possible hematological toxicity, unlike clozapine, JL 13 did not present sensitivity to peroxidase-induced oxidation. Moreover, its electrooxidation potential was close to that of loxapine and far from that of clozapine. Taking all these preclinical data into account, it appears that JL 13 is a promising atypical antipsychotic drug.
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PMID:JL 13, an atypical antipsychotic: a preclinical review. 1259 11