Comparison studies of tacrine and bis7-tacrine on the suppression of scopolamine-induced behavioral changes and inhibition of acetylcholinesterase in mice.

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.

• Authors: Si-Yuan Pan, Zhi-Ling Yu, Chun-Jing Xiang, Hang Dong, Hai-Yan Fang, Kam-Ming Ko
• Journal: Pharmacology (Pharmacology) Vol. 83 Issue 5 Pg. 294-300 ( 2009) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 19365154 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 S. Karger AG, Basel.

Chemical References

• 1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
• Cholinesterase Inhibitors
• Tacrine
• Scopolamine
• Acetylcholinesterase

Topics

• Acetylcholinesterase (blood, metabolism)
• Animals
• Avoidance Learning (drug effects)
• Brain (drug effects, metabolism)
• Cholinesterase Inhibitors (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Male
• Mice
• Mice, Inbred ICR
• Motor Activity (drug effects)
• Scopolamine (administration & dosage, pharmacology)
• Tacrine (administration & dosage, analogs & derivatives, pharmacology)