Pan SY, Yu ZL, Xiang CJ, Dong H, Fang HY, Ko KM
Department of Pharmacology, Beijing University of Chinese Medicine, Beijing
 School of Chinese Medicine, Hong Kong Baptist University
 Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China
Effects of the cholinesterase inhibitors tacrine and bis(7)- tacrine (0.25–20 µmol/kg, s.c.) on locomotor activity and passive-avoidance response were investigated in mice treated with scopolamine (SCP, 1 or 5 µmol/kg, i.p.), using an open-field test and step-through task with a 24-hour retention interval. Drugs were given 30 min prior to the first session. During the acquisition session, SCP treatment increased the locomotor activity (10–16%). Tacrine, but not bis(7)-tacrine, cotreatment significantly reduced the locomotor activity by 23 or 27%, when compared with the SCP-treated control mice. In the step-through task, tacrine or bis(7)-tacrine coadministration dose-dependently attenuated the increase in the number of footshocks (by 50 or 58%) in SCP-treated mice. The lowest dose of tacrine and bis(7)-tacrine for prolonging the retention latency (up to 500%) in SCP-treated mice was 5 and 1 umol/kg, respectively. Tacrine and bis(7)-tacrine inhibited brain acetylcholinesterase (AChE) activity 15 min (but not 30 min) after the drug administration in mice. At the same dose of 20 umol/kg, the bis(7)-tacrine-induced AChE inhibition in serum was 14-fold higher than that of tacrine. The results indicated that bis(7)-tacrine was less potent than tacrine in causing motor dysfunction. However, bis(7)-tacrine was more potent than tacrine in the cognitive enhancement of SCP-induced memory loss and in AChE inhibition.