Dopaminergic and ligand-independent activation of steroid hormone receptors

Neal Modi*, Tianlin Yuan*, Dr. Todd Parrish**, Dr. Xue Wang**, Dr. Darren Gitelman** * Illinois Mathematics and Science Academy ** Northwestern University, Feinberg School of Medicine, Department of Radiology Abstract Parkinson’s disease (PD) is a chronic movement disorder that occurs when nigrostriatal dopaminergic neurons within the Basal Ganglia Network (BGN) are damaged or destroyed, causing motor and cognitive disabilities. Motor disabilities can be measured by the Unified Parkinson’s Disease Rating Scale (UPDRS-III). PD currently has […]

In clinical trials of pramipexole, however, and despite clear orthostatic effects in normal volunteers, the reported incidence of clinically significant orthostatic hypotension was not greater among those assigned to pramipexole tablets than among those assigned to placebo. This result, especially with the higher doses used in Parkinson's disease, is clearly unexpected in light of the previous experience with the risks of dopamine agonist therapy. While this finding could reflect a unique property of pramipexole, it might also be explained by the conditions of the study and the nature of the population enrolled in the clinical trials. Patients were very carefully titrated, and patients with active cardiovascular disease or significant orthostatic hypotension at baseline were excluded. Also, clinical trials in patients with RLS did not incorporate orthostatic challenges with intensive blood pressure monitoring done in close temporal proximity to dosing.

Based on studies in which high doses of levodopa and/or carbidopa were administered, a significant proportion of rats and mice given single oral doses of levodopa of approximately 1500-2000 mg/kg are expected to die. A significant proportion of infant rats of both sexes are expected to die at a dose of 800 mg/kg. A significant proportion of rats are expected to die after treatment with similar doses of carbidopa. The addition of carbidopa in a 1:10 ratio with levodopa increases the dose at which a significant proportion of mice are expected to die to 3360 mg/kg.

Dopaminergic and ligand-independent activation of steroid hormone receptors

dopaminergic and ligand-independent activation of steroid hormone receptors

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dopaminergic and ligand-independent activation of steroid hormone receptorsdopaminergic and ligand-independent activation of steroid hormone receptorsdopaminergic and ligand-independent activation of steroid hormone receptorsdopaminergic and ligand-independent activation of steroid hormone receptorsdopaminergic and ligand-independent activation of steroid hormone receptors

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