Ganstigmine (
CHF2819) is a novel, orally active
acetylcholinesterase inhibitor that induces a stimulation of brain
cholinergic transmission. In vivo studies show that, in rat prefrontal cortex, extracellular
acetylcholine (ACh) concentrations are significantly increased either after local (1 and 10 microM) or oral (1.5 and 3 mg/kg) administration. Moreover, repeated oral treatment (six consecutive days; 3 mg/kg) with
ganstigmine significantly increases basal extracellular concentrations of ACh in rat prefrontal cortex. Then, acute
ganstigmine administration induces a significant increase in extracellular ACh concentrations (actual values) with respect to the last sample in
ganstigmine-treated rats. Concentrations of
serotonin (5-HT) and
noradrenaline (NA) are not affected by any oral dose of
ganstigmine (1.5 and 3 mg/kg) used. Moreover, levels of
dopamine (DA) and metabolites are not modified either. Basal extracellular concentrations of
5-HT, NA, DA and metabolites are not affected by repeated (six consecutive days)
ganstigmine treatment (3 mg/kg). Furthermore, there is no effect of the challenge dose of
ganstigmine (3 mg/kg) on
5-HT, NA, DA and metabolites levels. Finally,
ganstigmine reverses the
scopolamine-induced deficits of habituation and non-spatial working memory in rats. Taken together, these findings suggest that
ganstigmine appears to be a suitable candidate for the treatment of the
cholinergic deficit in patients with
Alzheimer's disease.