Effect of T-588, a novel cognitive enhancer, on scopolamine-induced EEG slowing

Effects of T-588 on scopolamine-induced electroencephalography (EEG) changes in rabbits were investigated. Scopolamine (0.05 mg/kg, i.v.) increased the appearance rate of delta waves (0-4Hz) in frontal cortex, amygdala and hippocampus, and decreased the appearance rate of beta waves (13-25Hz) in frontal cortex and amygdala. High voltage spindles (HVS) were observed in the alpha frequency band (8-13Hz) in frontal cortex and hippocampus. T-588 (0.1 mg/kg, i.v.) administered 15 min before the scopolamine treatment significantly inhibited EEG slowing in frontal cortex and amygdala, but did not completely suppress the appearance rate of alpha waves. Tacrine (1 mg/kg, i.v.), a cholinesterase inhibitor, also inhibited scopolamineinduced EEG slowing in frontal cortex and amygdala. T-588 alone had no effect on spontaneous EEG, but tacrine (1 mg/kg, i.v.) itself increased the appearance rate of beta waves in frontal cortex and amygdala. These results suggest that T-588 might enhance cholinergic nervous system and be an useful agent for therapy of Alzheimers disease.