Regional Cyclic Nucleotide Phosphodiesterase Activity in Cat Central Nervous System: Effects of Benzodiazepines

Summary

Cyclic AMP and cGMP phosphodiesterase activity was found in the supernatant fraction of 15 freshly dissected regions of the cat central nervous system. Highest activity was found in the cerebral cortex; lesser activity was observed in other regions of the CNS. Diazepam and medazepam HCl were as active as the known cAMP-PD inhibitors papaverine and dipyridamole in cat cortex, rat brain, and mouse neuroblastoma cells. The diazepam metabolites N-demethyldiazepam, N-methyloxazepam, and oxazepam showed less inhibition of PD than the parent compound. No evidence was found for a regionally specific biochemical action of the benzodiazepines involving intracellular cAMP or cGMP.

We thank Dr. A. Blume, Roche Institute of Molecular Biology, for the neuroblastoma cells. We also thank Gloria Wiggan for the cGMP assay, and Frank Zabransky for the cat brain samples.