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.
Cunha
G M A
GM
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo, 1127 Fortaleza, Brazil, CEP 60430-270. gmatos@ufc.br
Farias
P A M
PA
Viana
G S B
GS
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001362:Avoidance Learning / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced* / Q000523:psychology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000523:psychology; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000633:toxicity; D010095:Oxotremorine / Q000494:pharmacology; D010431:Pentoxifylline / Q000494:pharmacology*; D010862:Pilocarpine / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012601:Scopolamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D014202:Tremor / Q000139:chemically induced / Q000517:prevention & control
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D010095:Oxotremorine; D012601:Scopolamine; D000110:Acetylcholinesterase; D010431:Pentoxifylline