Manipulation of endogenous adenosine affects seizure susceptibility

Thomas F. Murray, Ge Zhang, Paul H. Franklin

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Abstract

A1 adenosine receptors in rat prepiriform cortex (PPC) play an important role in the inhibition of bicuculline methiodide (BMI)-induced convulsions. In the present study, we evaluated the manipulation of endogenous adenosine in this brain area as a strategy to effect seizure suppression. All compounds evaluated were unilaterally microinjected into the PPC. Focal administration of 5' NH25'dADO and dilazep were found to be highly efficacious as anticonvulsants with respective ED50 values of 2.6 ± 0.8, and 5.6 ± 1.6 nmol. In contrast, 2'DCF was both less potent and less efficacious. These results suggest that accumulation of endogenous adenosine may contribute to seizure suppression, and that adenosine kinase and adenosine transport may play a pivotal role in the regulation of extracellular levels of adenosine in the CNS.

Original languageEnglish (US)
Pages (from-to)410-415
Number of pages6
JournalDrug Development Research
Volume28
Issue number3
DOIs
StatePublished - Mar 1993
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Drug Discovery

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