Effects of nootropic drugs in a scopolamine-induced amnesia model in mice.

Scopolamine (3 mg/kg IP) given before an acquisition trial, reduced the retention of a one-trial passive avoidance "step through" response in mice. A single administration of cholinergic agonists such as oxotremorine, BM-5, or arecoline, antagonized this amnesic effect of scopolamine. A significant anti-amnesic effect was also found with nootropic drugs such as piracetam and ucb L059, whereas ucb L060 (the enantiomer of ucb L059), oxiracetam and rolziracetam were shown to be ineffective. Moreover, ucb L059, administered twice daily for 3 days, counteracted the amnesic effects of scopolamine completely, whereas ucb L060 was again inactive. The results demonstrate that: (a) this model of impaired cognition by scopolamine is able to discriminate between closely related chemical substances and even stereoisomers; and (b) nootropic drugs, such as ucb L059, are more effective after repeated rather than after acute administration.