Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 11, Issue 7, Pages 1299-1310Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0968-0896(02)00648-X
Keywords
-
Funding
- NIEHS NIH HHS [ES10804] Funding Source: Medline
- NINDS NIH HHS [NS411083] Funding Source: Medline
Ask authors/readers for more resources
Adenosine receptor antagonists that are selective for the A(2A) receptor subtype (A(2A) antagonists) are under investigation as possible therapeutic agents for the symptomatic treatment of the motor deficits associated with Parkinson's disease (PD). Results of recent studies in the MPTP mouse model of PD suggest that A(2A) antagonists may possess neuroprotective properties. Since monoamine oxidase B (MAO-B) inhibitors also enhance motor function and reduce MPTP neurotoxicity, we have examined the MAO-B inhibiting properties of several A(2A) antagonists and structurally related compounds in an effort to determine if inhibition of MAO-B may contribute to the observed neuroprotection. The results of these studies have established that all of the (E)-8-styryl-xanthinyl derived A(2A) antagonists examined display significant MAO-B inhibitory properties in vitro with K-i values in the low muM to nM range. Included in this series is (E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methylxanthine (KW-6002), a potent A(2A) antagonist and neuroprotective agent that is in clinical trials. The results of these studies suggest that MAO-B inhibition may contribute to the neuroprotective potential of A(2A) receptor antagonists such as KW-6002 and open the possibility of designing dual targeting drugs that may have enhanced therapeutic potential in the treatment of PD. (C) 2003 Elsevier Science Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available