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)

Until a few years ago, the anti-parkinsonian effect of amantadine hydrochloride (AHCl) and amantadine sulfate (AS) could not be explained. The beneficial effect of amantadine, which has been observed for a long time, may be connected with its site of action at the glutamatergic excitatory transmitter system, i.e. the N-methyl-D-aspartate receptor. A clear distinction can be made between AHCl and AS with regard to this pharmacokinetic profile. Therefore, AS can be administered in higher doses than AHCl and is thus more effective. A major advantage of AS is that it can also be given intravenously. Yet so far it is marketed only in twelve countries of the world. Intravenous infusions of AS permit the treatment of patients with aphagia during akinetic crises and when L-dopa and dopaminergic agonists are not tolerated in the akinetic terminal stage. Amantadine has the best ratio of therapeutic effects to side effects when compared with the other anti-parkinsonian drugs currently used. Long-term treatment with amantadine may have a considerable L-dopa saving effect. Given in higher doses, amantadine may permit a drastic reduction of L-dopa dosis and dopaminergic agonists so that the well known side effects of such drugs disappear. In addition, some authors assume a neuroprotective action of amantadine. Unlike L-dopa and dopaminergic agonists, AS does not produce hemiballism or dystonia.
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PMID:Twenty-five years of amantadine therapy in Parkinson's disease. 882 Oct 75

Dystonia is a common manifestation in Wilson's disease (WD). The striatum, especially the putamen, has been considered to be responsible for dystonia. We reported 3 patients who developed acute generalized dystonia and akinetic rigid syndrome following an initial therapy with d-penicillamine 125-500 mg daily. Brain MRI revealed lesions in the thalamus and the brainstem, particularly the tegmentum, and the basis pontis in addition to the basal ganglion lesions. After the episode, 1 patient continued to receive d-penicillamine therapy and 2 changed to zinc sulfate treatment. The generalized dystonia improved in the following 3 months and 3 years respectively in 2 patients. Follow-up brain MRI of these 2 patients revealed that the lesions in the thalamus and brainstem disappeared or resolved almost completely. From these data, acute generalized dystonia with brainstem and thalamic lesions may occur in WD patients after an initial d-penicillamine therapy. Furthermore, the dystonia may resolve following the disappearance of the brainstem and thalamic lesions.
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PMID:Acute dystonia with thalamic and brainstem lesions after initial penicillamine treatment in Wilson's disease. 947 21

Idiopathic Parkinson's disease (IPD) represents a common neurodegenerative disorder. An estimated 2% of the U.S. population, age 65 and older, develops IPD. The number of IPD patients will certainly increase over the next several decades as the baby-boomers gradually step into this high-risk age group, concomitant with the increase in the average life expectancy. While many studies have suggested that industrial chemicals and pesticides may underlie IPD, its etiology remains elusive. Among the toxic metals, the relationship between manganese intoxication and IPD has long been recognized. The neurological signs of manganism have received close attention because they resemble several clinical disorders collectively described as extrapyramidal motor system dysfunction, and in particular, IPD and dystonia. However, distinct dissimilarities between IPD and manganism are well established, and it remains to be determined whether Mn plays an etiologic role in IPD. It is particularly noteworthy that as a result of a recent court decision, methylcyclopentadienyl Mn tricarbonyl (MMT) is presently available in the United States and Canada for use in fuel, replacing lead as an antiknock additive. The impact of potential long-term exposure to low levels of MMT combustion products that may be present in emissions from automobiles has yet to be fully evaluated. Nevertheless, it should be pointed out that recent studies with various environmental modeling approaches in the Montreal metropolitan (where MMT has been used for more than 10 years) suggest that airborne Mn levels were quite similar to those in areas where MMT was not used. These studies also show that Mn is emitted from the tail pipe of motor vehicles primarily as a mixture of manganese phosphate and manganese sulfate. This brief review characterizes the Mn speciation in the blood and the transport kinetics of Mn into the central nervous system, a critical step in the accumulation of Mn within the brain, outlines the potential susceptibility of selected populations (e.g., iron-deficient) to Mn exposure, and addresses future research needs for Mn.
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PMID:Manganese: brain transport and emerging research needs. 1085 40

The pathophysiology of various types of dyskinesias, including dystonias, is poorly understood. Clinical and epidemiological studies in humans revealed that the severity of dyskinesias and the frequency of paroxysmal forms of the disease are altered by factors such as the onset of puberty, pregnancy, cyclical changes and stress, indicating an underlying hormonal component. The dystonic phenotype in the dt(sz) hamster, a genetic animal model of paroxysmal dystonia, has been suggested to be based on a deficit of striatal gamma-aminobutyric acid (GABA)ergic interneurons and changes in the GABA(A) receptor complex. In this animal model, hormonal influences seem to be also involved in the pathophysiology, but an influence of peripheral sex hormones has already been excluded. Possibly, neurosteroids as endogenous regulators of the GABA(A) receptor may be critically involved in the pathophysiology of dystonia in this animal model. Therefore, in the present study, the effects of the neurosteroids allopregnanolone acetate and allotetrahydrodeoxycorticosterone (THDOC), representing positive modulators of the GABA(A) receptor, as well as of the negative GABA(A) receptor modulators pregnenolone sulfate and dehydroepiandrosterone (DHEA), on severity of dystonia were examined in dt(sz) hamsters after acute intraperitoneal injections. Allopregnanolone acetate and THDOC exerted a moderate reduction of dystonia, whereas pregnenolone sulfate and DHEA had no significant effects. Although the effects of allopregnanolone acetate and THDOC were moderate and short-lasting, the present results suggest that changes in neurosteroid levels might be involved in the initiation of dystonic episodes. Future studies have to include measurements of brain neurosteroid levels as well as of chronic neurosteroid administrations to clarify the pathophysiological role and therapeutic potential of neurosteroids in dystonia.
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PMID:Acute effects of neurosteroids in a rodent model of primary paroxysmal dystonia. 1755 99