Evidence for the involvement of the muscarinic cholinergic system in the central actions of pentoxifylline

This study shows that pentoxifylline (ptx), a xanthine derivative, significantly attenuates scopolamine-induced memory impairment in rats, as demonstrated in a passive avoidance task (50 mg/kg intraperitoneally [i.p.]) and in an elevated T-maze (10 and 50 mg/kg i.p.). Ptx (25, 50 and 100 mg/kg i.p.) also potentiates oxotremorine-induced tremors in mice, in a dose-dependent manner, and this effect was completely prevented by atropine. In addition, ptx (50 and 100 mg/kg i.p.) increased the number of animals developing pilocarpine-induced seizures, and potentiated the latency to the first pilocarpine-induced convulsion. Hippocampus homogenates from rats treated with ptx (100 mg/kg) for 1 week and sacrificed 15 min after the last injection showed a significant decrease in the muscarinic receptor numbers, indicative of a downregulation phenomenon. Similar effects were observed when assays were performed 24 h after the last ptx injection (10 and 50 mg/kg i.p.), but not after 72 h. Additionally, in vitro assays showed that ptx inhibits acetylcholinesterase activity in a dose-dependent manner when incubated with homogenates from rat hippocampus. Our data suggest that the muscarinic agonist effect of ptx could possibly depend on factors such as endogenous cholinergic activity. (C) 2002 Lippincott Williams Wilkins.