Comparison Studies of Tacrine and Bis(7)-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 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 μmol/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 μmol/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.

Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice

“…The step-through test was performed to examine memory acquisition as previously described [ 35 , 36 ]. Briefly, the test included a training trial on the first day and retention trial on the second day.…”

Molecular Targets of Bis (7)-Cognitin and Its Relevance in Neurological Disorders: A Systematic Review

“…Three studies included both in vitro and in vivo approaches. The molecular target that was primarily studied was AChE in 11 studies (Li et al, 1999; Wang et al, 1999b; Ros et al, 2001; Hu et al, 2002, 2015b; Fu et al, 2006; Yu et al, 2008; Pan et al, 2009; Bolognesi et al, 2010; Rizzo et al, 2011; Qian et al, 2014), followed by the NMDA receptor ( n = 8) (Bai-fang et al, 2001; Li et al, 2005, 2007b; Luo et al, 2007; Liu et al, 2008a,b; Zhang et al, 2011; Liu and Li, 2012). The BChE was under scrutiny in five studies (Wang et al, 1999b; Hu et al, 2002; Bolognesi et al, 2010; Rizzo et al, 2011; Qian et al, 2014), the BACE-1 in four studies (Fu et al, 2008, 2009; Bolognesi et al, 2010; Rizzo et al, 2011), the GABA receptor in three studies (Li et al, 1999, 2007a; Zhou et al, 2009), the nitric oxide synthase (NOS) in two studies (Li et al, 2006, 2007b), the Kv4.2 potassium channels also in two studies (Nie et al, 2007; Li et al, 2010), the serotonin receptor 5-HT 3 in one study (Luo et al, 2004), the α-secretase also in one study (Fu et al, 2009), the L-type voltage-dependent Ca 2+ channels in one study (Fu et al, 2006), and the choline acetyl transferase in one study as well (Liu et al, 2000).…”

“…Apoptosis (Han et al, 2000; Fu et al, 2007; Zhao et al, 2008; Fang et al, 2010), neuritogenesis, and neurite outgrowth (Chang et al, 2015; Hu et al, 2015a), long-term potentiation (Chang et al, 2015), amyloid beta (Aβ) aggregation and toxicity (Chang et al, 2015; Hu et al, 2015a), cell toxicity (Xiao et al, 2000), and retinal ischaemia (Li et al, 2014) were those biological processes where the effect of B7C was examined. The effect of B7C on spatial learning and memory was evaluated using the Morris water maze test in six studies (Wang et al, 1999a; Liu et al, 2000; Han et al, 2012; Shu et al, 2012; Chang et al, 2015; Hu et al, 2015b), the step-through task was used to measure the passive-avoidance response in two studies (Pan et al, 2007, 2009), the open field test was used also in two studies (Pan et al, 2009, 2011), and the novel object recognition test was used in one study (Han et al, 2012).…”

“…Several studies (see Table 2) have already demonstrated the effect of B7C on the inhibition of AChE in a selective manner and at lower concentration than tacrine (Li et al, 1999; Wang et al, 1999b; Ros et al, 2001; Hu et al, 2002, 2015b; Fu et al, 2006; Yu et al, 2008; Pan et al, 2009; Bolognesi et al, 2010; Rizzo et al, 2011; Qian et al, 2014). Drugs that inhibit AChE keep the ACh levels high in the synaptic cleft, thereby stimulating cholinergic transmission in regions of the forebrain that compensate for the loss of cells (Muñoz-Ruiz et al, 2005; Colović et al, 2013).…”