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  • Title: Comparison studies of tacrine and bis7-tacrine on the suppression of scopolamine-induced behavioral changes and inhibition of acetylcholinesterase in mice.
    Author: Pan SY, Yu ZL, Xiang CJ, Dong H, Fang HY, Ko KM.
    Journal: Pharmacology; 2009; 83(5):294-300. PubMed ID: 19365154.
    Abstract:
    Effects of the cholinesterase inhibitors tacrine and bis(7)- tacrine (0.25-20 micromol/kg, s.c.) on locomotor activity and passive-avoidance response were investigated in mice treated with scopolamine (SCP, 1 or 5 micromol/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 micromol/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 micromol/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.
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