Manipulation of endogenous adenosine affects seizure susceptibility

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

doi:10.1002/ddr.430280341

Manipulation of endogenous adenosine affects seizure susceptibility

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

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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 language	English (US)
Pages (from-to)	410-415
Number of pages	6
Journal	Drug Development Research
Volume	28
Issue number	3
DOIs	https://doi.org/10.1002/ddr.430280341
State	Published - Mar 1993
Externally published	Yes

All Science Journal Classification (ASJC) codes

Drug Discovery

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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.",

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AU - Murray, Thomas F.

AU - Zhang, Ge

AU - Franklin, Paul H.

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N2 - 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.

AB - 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.

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