Partially purified extracts of bovine brain were previously found to inhibit competitively the binding of [3H]-
diazepam to rat brain synaptosomal membranes. The
purines inosine and
hypoxanthine were subsequently identified as the compounds responsible for this inhibitory activity. Intracerebroventricular administration of
inosine to mice of the C3H/HEN and NIH general purpose strains caused a dose- and time-dependent increase in the latency to clonicotonic
seizures produced by intraperitoneal administration of the
convulsant pentylenetetrazole. Intracerebroventricular administration of equimolar doses of
2'-deoxyinosine, which is more potent than
inosine in inhibiting the binding of [3H]
diazepam in vitro, significantly increased
pentylenetetrazole-evoked seizure latency. In contrast, both
7-methylinosine and
thymidine were ineffective in inhibiting the in vitro binding of [3H]
diazepam and increasing the latency to
pentylenetetrazole-induced
seizures in vivo. These results suggest that endogenously occurring
purines such as
inosine exhibit
diazepam like effects when administered intracerebroventricularly, and these effects may be related to the interaction of
inosine and related compounds with
benzodiazepine receptors in the central nervous system.