DM235 (sunifiram), a new compound structurally related to piracetam, prevented the amnesia induced by scopolamine (1.5 mg kg–1 i.p.), after intraperitoneal (0.001–0.1 mg kg–1) or oral (0.01–0.1 mg kg–1) administration, as shown by a passive avoidance test in mice. The antiamnesic effect of DM235 was comparable to that of well-known nootropic drugs such as piracetam (30–100 mg kg–1 i.p.), aniracetam (100 mg kg–1 p.o.) or rolipram (30 mg kg–1 p.o.). DM235 also prevented mecamylamine (20 mg kg–1 i.p.)-, baclofen (2 mg kg–1 i.p.)- and clonidine (0.125 mg kg–1 i.p.)-induced amnesia in the same test. In the Morris water maze test with rats, scopolamine (0.8 mg kg–1 i.p.) inhibited the reduction of escape latency in both acquisition and retention/retraining tests. DM235 (0.1 mg kg–1 i.p.), 20 min before each daily acquisition training, prevented the scopolamine-induced memory impairment. DM235 (1 mg kg–1 i.p.) also reduced the duration of pentobarbitone-induced hypnosis in mice without modifying the induction time of hypnosis. At the highest effective doses, the investigated compound neither impaired motor coordination (rota-rod test), nor modified spontaneous motility and inspection activity (Animex and hole board tests).
These results indicate that DM235, a compound structurally related to piracetam, is a novel nootropic endowed with the capability to prevent cognitive deficits at very low doses. Indeed, its potency is about 1,000 times higher than that of the most active piracetam-like compounds.