Purinergic inhibition of diazepam binding to rat brain (in vitro)

Our recent report that the endogenous purines inosine and hypoxanthine competitively inhibit [³H] diazepam binding to rat brain synaptosomal membranes (1,2) has now been confirmed (3). We now report that a wide spectrum of purines are able to inhibit specific [³H] diazepam binding while pyrimidines are inactive. Preliminary structure activity relationships indicate that the 2′-deoxypurines are more potent in diazepam binding inhibition as are the l-methyl compounds, whereas the 7-methyl purines are inactive. Data are also presented which show that the xanthine stimulants caffeine, theophylline, and theobromine as well as the central nervous system convulsant pentylenetetrazol all competitively inhibit [³H] diazepam binding.