Research PapersEvidence for the involvement of the muscarinic cholinergic system in the central actions of pentoxifyllineCunha, G.M.A.; Farias, P.A.M.; Viana, G.S.B.Author Information Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo, 1127 Fortaleza, Brazil, CEP 60430-270 Correspondence to G.M.A. Cunha, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo, 1127 Fortaleza, Brazil, CEP 60430-270. E-mail: [email protected] Received 16 May 2001 accepted as revised 11 December 2001 Behavioural Pharmacology: March 2002 - Volume 13 - Issue 2 - p 149-156 Buy Abstract 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. © 2002 Lippincott Williams & Wilkins, Inc.