Pharmacological effects of indeloxazine, a new cerebral activator, on brain functions distinct from other cerebral metabolic enhancers

Abstract

The effects of indeloxazine hydrochloride [(+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride, YM-08054], a new cerebral metabolic enhancer, on learned behavior and central monoaminergic function were compared to those of other cerebral metabolic enhancers in animals. Indeloxazine enhanced passive learned behaviour in rats and ameliorated cerebral ischemia-induced learned disturbances in gerbils. Reserpine-induced hypothermia in mice, ponto-genicullo-occipital (PGO) waves in reserpinized cats and caudate spindle activity in cats were reduced by the administration of indeloxazine, suggesting that the drug possesses facilitatory effects on central monoaminergic systems. In contrast, piracetam, calcium-hopantenate, idebenone and bifemelane had no significant effect on learned behavior or central monoaminergic function, with the exception of bifemelane which antagonized reserpine-induced hypothermia. These results are in contrast to the findings that all tested cerebral metabolic enhancers, including indeloxazine, prolonged the survival time of mice subjected to anoxia. The greater effect of indeloxazine to other cerebral metabolic enhancers, in facilitating learned behavior, may be attributable to its broader effects on central monoaminergic systems.