The low KM-phosphodiesterase inhibitor denbufylline enhances neuronal excitability in guinea pig hippocampus in vitro

The actions of the phosphodiesterase inhibitor denbufylline on the
excitability of hippocampal neurons were investigated by means of
extracellular and intracellular recordings. Denbufylline, which has
been shown to selectively inhibit a low KM,
Ca2+/calmodulin-independent phosphodiesterase isozyme,
concentration-dependently increased the amplitude of the
extracellularly recorded CAI population spike evoked by electrical
stimulation of the Schaffer collateral/commissural pathway.
Concentration-response-curves yielded an EC50 for denbufylline of
0.76 M. In comparison, the nonselective phosphodiesterase inhibitor
3-isobutyl-lmethylxanthine (IBMX) also produced an increase in the
amplitude of the population spike. From the
concentration-response-curve, which was steeper than that of
denbufylline, an EC50 for IBMX of 1.04 M was obtained. However,
despite their similar EC50 values, denbufylline was found to be
significantly more potent at lower concentrations (