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.
Current Topics in Medicinal Chemistry
Title: Anticonvulsant and Antinociceptive Actions of Novel Adenosine Kinase Inhibitors
Volume: 5 Issue: 1
Author(s): Steve McGaraughty, Marlon Cowart, Michael F. Jarvis and Robert F. Berman
Affiliation:
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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Cite this article as:
McGaraughty Steve, Cowart Marlon, Jarvis F. Michael and Berman F. Robert, Anticonvulsant and Antinociceptive Actions of Novel Adenosine Kinase Inhibitors, Current Topics in Medicinal Chemistry 2005; 5 (1) . https://dx.doi.org/10.2174/1568026053386845
DOI https://dx.doi.org/10.2174/1568026053386845 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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