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Medientyp: E-Artikel Titel: Effects of metrifonate and tacrine in the spatial morris task and modified irwin test: Evaluation of the efficacy/safety profile in rats Beteiligte: Blokland, Arjan; Hinz, Volker; Schmidt, Bernard H. Erschienen: Wiley, 1995 Erschienen in: Drug Development Research Sprache: Englisch DOI: 10.1002/ddr.430360403 ISSN: 0272-4391; 1098-2299 Schlagwörter: Drug Discovery Entstehung: Anmerkungen: Beschreibung: <jats:title>Abstract</jats:title><jats:p>In the present study we investigated the efficacy/safety profile of the cholinesterase inhibitors metrifonate (MTF) and tacrine [tetrahydroaminoacridine (THA)]. We tested the efficacy of MTF (12, 39, and 120 μmol/kg po) and THA (1.3, 4.3, and 13 μmol/kg po) in the spatial Morris task in 19‐month‐old rats. The modified Irwin test was used to evaluate the safety of both drugs, using in 19‐month‐old rats. In this observation test, higher doses of MTF (39, 120, and 390 μmol/kg) and THA (4.3, 13, and 43 μmol/kg) were tested. MTF was found to improve the performance of rats in the spatial Morris task. Independent of dose, MTF‐treated rats performed better than vehicle‐treated rats in the Morris task during the 2nd week of testing. THA treatment (1.3 μmol/kg) had only a minor effect on the spatial discrimination performance, i.e., effect on the probe trial after 2 weeks of training. In the modified Irwin test, both MTF and THA dose dependently induced side effects which were classified as being typically cholinergic. The threshold dose for the occurrence of side effects for acutely administered MTF and THA was 39 and 4.3 μmol/kg, respectively. Remarkably, repeated administration of 390 μmol/kg MTF (5 day treatment) resulted in fewer side effects. This was not observed for THA treatment. The data of the present study indicate that the efficacy/safety profile of MTF is more favorable than that of THA. © 1995 Wiley‐Liss, Inc.</jats:p>