Comparison studies of tacrine and bis7-tacrine on the suppression of scopolamine-induced behavioral changes and inhibition of acetylcholinesterase in mice.
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.
Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, SAR, China. siyuan-pan@163.com
Si-Yuan
SY
Pan
Zhi-Ling
ZL
Yu
Chun-Jing
CJ
Xiang
Hang
H
Dong
Hai-Yan
HY
Fang
Kam-Ming
KM
Ko
D000110:Acetylcholinesterase / Q000097:blood* / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D012601:Scopolamine / Q000008:administration & dosage / Q000494:pharmacology*; D013619:Tacrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*
C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D002800:Cholinesterase Inhibitors; D013619:Tacrine; D012601:Scopolamine; D000110:Acetylcholinesterase