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)

The effect of the adenosine A(2A) receptor agonist CGS 21680 (2-carboxyethyl)phenylethylamino]-5'-N-ethylcarbonyamido-ade nosine) on severity of dystonia was examined in genetically dystonic hamsters which exhibit attacks of dystonic and choreoathetotic disturbances in response to mild stress. CGS 21680 significantly reduced the severity of dystonia (0.5, 1.0 and 2.0 mg/kg i.p.). The marked antidystonic effects of CGS 21680 in the hamster model suggest that this compound may represent an interesting candidate for the therapy of paroxysmal dystonia. Furthermore, the present data indicate that the precipitating effect of caffeine in patients with paroxysmal dystonia is probably due to its adenosine receptor antagonistic action.
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PMID:CGS 21680 exerts marked antidystonic effects in a genetic model of paroxysmal dyskinesia. 1099 95

1. Recent studies have shown beneficial effects of an adenosine A(2A) receptor agonist in dt(sz) mutant hamsters, an animal model of paroxysmal dystonia, in which stress and consumption of coffee can precipitate dystonic attacks. This prompted us to examine the effects of adenosine receptor agonists and antagonists on severity of dystonia in dt(sz) hamsters in more detail. 2. The non-selective adenosine A(1)/A(2A) receptor antagonists, caffeine (10 - 20 mg kg(-1) i.p.) and theophylline (10 - 30 mg kg(-1) s.c.), worsened the dystonia in dt(sz) hamsters. 3. Aggravation of dystonia was also caused by the selective adenosine A(1)/A(2A) antagonist CGS 15943 (9-chloro2-2-furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine) at a dose of 30 mg kg(-1) i.p. and by the adenosine A(1) antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine; 20 - 30 mg kg(-1) i.p.), while the A(2) antagonist DMPX (3,7-dimethyl-1-propargylxanthine; 2 - 4 mg kg(-1) i.p.) and the highly selective A(2A) antagonist ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol; 2 - 5 mg kg(-1) i.p.) failed to exert any effects on dystonia. 4. In contrast to the antagonists, both the adenosine A(1) receptor agonist CPA (N(6)-cyclopentyladenosine; 0.1 - 1.0 mg kg(-1) i.p.) and the A(2A) agonist CGS 21680 (2p-(2carboxyethylphen-ethylamino-5'-N-ethylcarboxamindoadenosine; 0.1 - 2.0 mg kg(-1) i.p.) exerted a striking improvement of dystonia. 5. These data suggest that the precipitating effects of methylxanthines are, at least in part, related to their adenosine receptor antagonistic action. 6. Although adenosine receptor agonists can be regarded as interesting candidates for the therapy of paroxysmal dystonia, adverse effects may limit the therapeutic potential of adenosine A(1) agonists, while beneficial effects of the adenosine A(2A) agonist CGS 21680 were already found at well tolerated doses.
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PMID:Effects of adenosine receptor agonists and antagonists in a genetic animal model of primary paroxysmal dystonia. 1156 52

In patients with paroxysmal non-kinesigenic dyskinesias, episodes of dystonia can be provoked by stress and also by methylxanthines (e.g. caffeine), which inhibit adenosine A(1)/A(2A) receptors. In the dt(sz) mutant hamster, a model of this movement disorder, adenosine A(1) receptor antagonists were previously found to worsen dystonia, while adenosine A(1) and A(2A) receptor agonists exerted pronounced beneficial effects. Therefore, in the present study, adenosine receptor A(1) and A(2A) binding was determined by autoradiographic analyses in dt(sz) hamsters under basal conditions, i.e. in the absence of a dystonic attack, and in a group of mutant hamsters which exhibited severe stress-induced dystonic attacks prior to kill. In comparison with non-dystonic control hamsters, [(3)H]DPCPX (8-cyclopentyl-1,3-dipropylxanthine) binding to adenosine A(1) receptors and [(3)H]CGS 21680 (2p-(2carboxyethylphen-ethylamino-5'-N-ethlycarboxamindoadenosine) binding to adenosine A(2A) receptors were significantly lower throughout the brain of dystonic animals. Under normal resting conditions, mutant hamsters showed significant decreases in adenosine A(1) (-12 to-42%) and in A(2A) (-19 to-34%) receptor binding compared with controls. Stressful stimulation increased adenosine A(1) and A(2A) receptor binding in almost all brain regions in both control and dystonic hamsters. The stress-induced increase was more marked in mutant hamsters, leading to a disappearance of differences in most regions compared with stimulated controls, except the striatum. In view of previous findings of striking beneficial effects of adenosine A(1) and A(2A) receptor agonists and of striatal dysfunctions in the dt(sz) mutant, the reduced adenosine receptor binding may be an important factor in the pathogenesis of paroxysmal dystonia.
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PMID:Decreased adenosine receptor binding in dystonic brains of the dt(sz) mutant. 1596 Dec 43