Effects of the methylxanthine derivative pentoxifylline on benzodiazepine and muscarinic binding sites in rat cerebral cortex.

The subcutaneous injection of the methylxanthine derivative pentoxifylline (3,7, dimethyl-1-(5-oxo-hexyl)-xanthine) was able to induce, 3 h later, a significant reduction of benzodiazepine binding sites in rat cerebral cortex. When tested in vitro, pentoxifylline displaced 3H-flunitrazepam from specific binding sites in a competitive manner. For this effect pentoxifylline was about 10 times more potent than caffeine. When given in two daily injections for 5 days, pentoxifylline brought about a significant elevation in the number of cortical benzodiazepine binding sites. Neither acute nor chronic pentoxifylline treatment modified cortical muscarinic cholinergic binding sites. Pentoxifylline has negligible affinity for cortical muscarinic receptors in vitro. These results suggest that pentoxifylline is able to affect the cortical benzodiazepine receptors differentially, depending on time of drug administration.