Anticonvulsant and antinociceptive actions of novel adenosine kinase inhibitors

Steve McGaraughty, Marlon Cowart, Michael F. Jarvis, Robert F Berman

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)43-58
Number of pages16
JournalCurrent Topics in Medicinal Chemistry
Volume5
Issue number1
DOIs
StatePublished - 2005

ASJC Scopus subject areas

  • Medicine(all)
  • Chemistry(all)

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