103. Comparison studies of tacrine and bis(7)-tacrine on the suppression of scopolamine-induced behavioral changes and inhibition of acetylcholinesterase in mice.

Pan SY[1], Yu ZL[2], Xiang CJ[1], Dong H[2], Fang HY[1], Ko KM[3]

[1]Department of Pharmacology, Beijing University of Chinese Medicine, Beijing
[2] School of Chinese Medicine, Hong Kong Baptist University
[3] 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.