Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0233565 (bradykinesia)
 2,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine is an endogenous neuromodulator which alters neuronal excitability and firing rate. In recent years there has been growing interest in the manipulation of adenosine levels to understand the pathophysiology of various diseases. Dipyridamole (DPM) is a potent adenosine transport inhibitor that causes a several-fold increase in brain adenosine concentration. The present study was undertaken to investigate the effect of DPM on MPTP-induced neurotoxicity. Mice weighing 30 +/- 3 g were administered with MPTP (30 mg/kg, i.p.) daily for 5 days. DPM was given daily 1 h before MPTP in doses of 250, 500 and 1000 mg/kg body weight, (P.O.) respectively, in three different groups of mice for 7 days. Twenty four hours after the last dose of DPM, the animals were observed for neurobehavioral changes including locomotor activity and pole descending time. Immediately after behavioral studies, all the animals were sacrificed and brains were isolated for biochemical studies. The treatment of mice with MPTP or DPM individually produced no significant change in mobility or spasticity; however, the combination of these drugs produced significant bradykinesia. There was no incidence of mortality when the mice were treated with MPTP or DPM individually, though the combination of MPTP and DPM produced significant mortality which was proportional to the doses of the later drug. The treatment of mice with MPTP produced significant depletion of striatal dopamine and glutathione. Concomitant treatment of DPM with MPTP further reduced the striatal glutathione level without affecting dopamine. The result of this study shows the ability of DPM to potentiate MPTP-induced neurobehavioral toxicity and mortality in mice. Further studies are warranted to determine the role of adenosine in experimental and clinical Parkinson's disease.
 ...
PMID:Dipyridamole potentiates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental Parkinsonism in mice. 1859 Oct 87

Adenosine A2A receptors are predominantly localized on striatopallidal gamma-aminobutyric acid (GABA) neurons, where they are colocalized with dopamine D2 receptors and are involved in the regulation of movement. Adenosine A2A receptor antagonists have been evaluated as a novel treatment for Parkinson's disease and have demonstrated efficacy in a broad spectrum of pharmacological and toxicological rodent and primate models. Fewer studies have been performed to evaluate the efficacy of adenosine A2A receptor antagonists in genetic models of hypodopaminergic states. SCH 412348 is a potent and selective adenosine A2A receptor antagonist that shows efficacy in rodent and primate models of movement disorders. Here we evaluated the effects of SCH 412348 in the MitoPark mouse, a genetic model that displays a progressive loss of dopamine neurons. The dopamine cell loss is associated with a profound akinetic phenotype that is sensitive to levodopa (l-dopa). SCH 412348 (0.3-10mg/kg administered orally) dose dependently increased locomotor activity in the mice. Moreover, SCH 412348 retained its efficacy in the mice as motor impairment progressed (12-22 weeks of age), demonstrating that the compound was efficacious in mild to severe Parkinson's disease-like impairment in the mice. Additionally, SCH 412348 fully restored lost functionality in a measure of hind limb bradykinesia and partially restored functionality in a rotarod test. These findings provide further evidence of the anti-Parkinsonian effects of selective adenosine A2A receptor antagonists and predict that they will retain their efficacy in both mild and severe forms of motor impairment.
 ...
PMID:Effects of the selective adenosine A2A receptor antagonist, SCH 412348, on the parkinsonian phenotype of MitoPark mice. 2448 5