1.Parkinson disease drug screening based on the interaction between D(2) dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis.
Zheng ZHOU ; Jun-Ming LIAO ; Peng ZHANG ; Jun-Bao FAN ; Jie CHEN ; Yi LIANG
Protein & Cell 2011;2(11):899-905
Parkinson's disease is the second most common neurodegenerative disease in the world. Beta-arrestin-2 has been reported to be an important protein involved in D(2) dopamine receptor desensitization, which is essential to Parkinson's disease. Moreover, the potential value of pharmacological inactivation of G protein-coupled receptor kinase or arrestin in the treatment of patients with Parkinson's disease has recently been shown. We studied the interaction between D(2) dopamine receptor and beta-arrestin-2 and the pharmacological regulation of chemical compounds on such interaction using capillary zone electrophoresis. The results from screening more than 40 compounds revealed three compounds that remarkably inhibit the beta-arrestin-2/D(2) dopamine receptor interaction among them. These compounds are promising therapies for Parkinson's disease, and the method used in this study has great potential for application in large-scale drug screening and evaluation.
Arrestins
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antagonists & inhibitors
;
metabolism
;
Dopamine
;
metabolism
;
Dopamine Antagonists
;
therapeutic use
;
Dopamine D2 Receptor Antagonists
;
Drug Evaluation, Preclinical
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Electrophoresis, Capillary
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Humans
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Parkinson Disease
;
drug therapy
;
metabolism
;
pathology
;
Receptors, Dopamine D2
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metabolism
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Signal Transduction
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beta-Arrestin 2
;
beta-Arrestins
2.Comparative pharmacophore analysis of dual dopamine D2/5-HT(2A) receptor antagonists.
Acta Pharmaceutica Sinica 2009;44(3):314-320
Dual dopamine D2/5-HT2A receptor antagonists have potent activity and are referred to atypical antipsychotics due to their lower propensity to elicit EPS and their moderate efficacy toward negative symptoms. However, an on-going challenge in developing atypical antipsychotics drugs is to maintain the favorable profiles and avoid of cardiovascular risk. In this paper, comparative pharmacophore analysis of dual dopamine D2/5-HT2A receptor antagonists, hERG K+ channel blockers, and alA adrenoceptor antagonists is carried out, and the results could give some insight into multi-target drug design.
Adrenergic alpha-1 Receptor Antagonists
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Dopamine D2 Receptor Antagonists
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Drug Delivery Systems
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Drug Design
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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antagonists & inhibitors
;
chemistry
;
Molecular Conformation
;
Molecular Structure
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Receptor, Serotonin, 5-HT2A
;
chemistry
;
Receptors, Adrenergic, alpha-1
;
chemistry
;
Receptors, Dopamine D2
;
chemistry
;
Serotonin 5-HT2 Receptor Antagonists
;
Structure-Activity Relationship