Effects of the novel acetylcholinesterase inhibitor N-octyl-1,2,3,4-tetrahydro-9-aminoacridine on locomotor activity and avoidance learning in mice

The acetylcholinesterase reversible inhibitor N-octyl-1,2,3,4-tetrahydro-9- aminoacridine (THA-C8) is a new synthesized derivative of tacrine (THA) cha racterized by an alkyl chain in the molecular structure which ameliorates t he penetrability of the compound into the central nervous system. THA-C8 (0 .1-5 mg/kg) significantly reduced spontaneous locomotor activity in CD1 mic e at a dose of 3 mg/kg. Moreover, THA-C8 (0.2-2 mg/kg) significantly improv ed shuttle-box avoidance acquisition at doses (0.25, 0.3, 1 mg/kg) not affe cting locomotion and that are much lower than the doses reported to be effe ctive for THA in animal models. From the data reported it seems that the ne w compound could be interesting for therapeutic purposes. (C) 1999 Academic Press.