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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Anticonvulsant and Antinociceptive Actions of Novel Adenosine Kinase Inhibitors

Author(s): Steve McGaraughty, Marlon Cowart, Michael F. Jarvis and Robert F. Berman

Volume 5, Issue 1, 2005

Page: [43 - 58] Pages: 16

DOI: 10.2174/1568026053386845

Price: $65

Abstract

Adenosine (ADO) acts as an inhibitory neuromodulator throughout the central and peripheral nervous system and can regulate seizure and nociceptive activity. However, the positive actions of systemically administered ADO are usually accompanied by undesirable side effects such as hypomobility and cardio-suppression. Adenosine kinase (AK) is the primary metabolic enzyme regulating intra- and extracellular concentrations of ADO. We review the recent development of structurally novel nucleoside and nonnucleoside AK inhibitors that demonstrate high specificity for the AK enzyme. Several of these compounds have shown significant beneficial effects in animal models of epilepsy and pain with an improved preclinical therapeutic window over direct acting ADO receptor agonists.


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