Learning and memory effects of four newly-synthesized aniracetam analogues.

Four new analogues of the pyrolidine derivative with nootropic action--aniracetam--were synthesized using classical methods. The effects of the newly-synthesized compounds were tested using the step-through method for passive avoidance with negative reinforcement and the method of habituation of exploratory activity in the Opto-Varimex apparatus. Two series of experiments were performed using the step-through method: in one series aniracetam (Anc) and its analogues p-H and p-Cl were applied twice daily in a dose of 50 mg/kg for 7 days prior to the training session; retention tests were made 3 h, 24 h and 7 days after the training session. In the other series of experiments the Anc analogues p-P (in single daily doses of 10, 50 and 250 mg/kg) and p-F (in a single daily dose of 50 mg/kg) were applied for 5 days prior to the training session; memory tests were performed 24 h and 7 days after the training session. In one of the experimental series in Opto-Varimex, after 5-min recording of the horizontal, vertical and rotatory movements of each rat, the various groups of animals received 20, 100 or 300 mg/kg from each of the agents tested (Anc, p-Cl and p-H). Tests for habituation were performed 7 days later. The other series of experiments in Opto-Varimex included groups of rats receiving 50 mg/kg Anc, p-Cl and p-H twice daily for 7 days. The three types of movement were recorded for 5 min in the Opto-Varimex after the last dose of the substances tested. All substances were administered orally. The results obtained (longer time spent by the animals in the illuminated section when the step-through method was used and enhanced habituation in the Opto-Varimex experiments) suggest that the substances tested improve the memory, mainly through improving the process of consolidation of the memory traces.