title: Neurochemical and neurobehavioral effects of ganstigmine (CHF2819), a novel acetylcholinesterase inhibitor, in rat prefrontal cortex: an in vivo study.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, University of Foggia, Foggia, Italy. trabace@unifg.it
authors.forename: Luigia
authors.initials: L
authors.lastname: Trabace
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cassano
authors.forename: Marilena
authors.initials: M
authors.lastname: Colaianna
authors.forename: Silvia
authors.initials: S
authors.lastname: Castrignanò
authors.forename: Arcangela
authors.initials: A
authors.lastname: Giustino
authors.forename: Salvatore
authors.initials: S
authors.lastname: Amoroso
authors.forename: Luca
authors.initials: L
authors.lastname: Steardo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuomo
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D000284:Administration, Oral; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002219:Carbamates / Q000008:administration & dosage / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects*; D005110:Extracellular Space / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine; D012701:Serotonin / Q000378:metabolism