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Anticonvulsant and Antinociceptive Actions of Novel Adenosine Kinase Inhibitors

[ Vol. 5 , Issue. 1 ]

Author(s):

Steve McGaraughty, Marlon Cowart, Michael F. Jarvis and Robert F. Berman   Pages 43 - 58 ( 16 )

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.

, Anticonvulsant, and, Antinociceptive, Actions, of, Novel, Adenosine, Kinase, Inhibitors

Affiliation:

Neuroscience Research, Abbott Laboratories, R4PM, AP9-1, 100 Abbott Park Road, Abbott Park, IL 60064-6118, USA.



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