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 exhibited 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.
|Number of pages||4|
|State||Published - 1979|