Improvement of cognitive functions by the acetylcholine releaser SM 21

The effect of administration of SM 21 on memory processes was evaluated in the mouse passive avoidance and in the rat social learning tests. SM 21 (10–20 mg kg⁻¹ i.p.) prevented amnesia induced by scopolamine and dicyclomine as tested by the mouse passive avoidance test and prevented memory disruption by AF‐64A and benehexol ascertained by the rat passive avoidance test. Both SM 21 enantiomers were able to abolish dicyclomine‐induced amnesia in mice. SM 21, starting from the dose of 10 mg kg⁻¹ i.p., antagonized the memory impairment produced by mecamylamine, baclofen, and diphenhydramine in mice, as well as amnesia induced by diazepam in rats. SM 21, at doses ranging between 10 and 30 mg kg⁻¹ i.p., prevented memory reduction in mice by hypoxia in the passive avoidance test. In the social learning test, SM 21 (10 mg kg⁻¹ i.p.) injected in adult rats reduced the duration of active exploration of a familiar partner in the second session of the test. SM 21 prevented amnesia in both mice and rats comparable to that of the cholinesterase inhibitor physostigmine (0.2 mg kg⁻¹ i.p.), the M1 selective agonist AF‐102B (10 mg kg⁻¹ i.p.), and the nootropic drug piracetam (30 mg kg⁻¹ i.p.). These results demonstrated the ability of SM 21 to modulate memory functions and suggests that SM 21 could be useful in the treatment of cognitive deficits. Drug Dev. Res. 47:118–126, 1999. © 1999 Wiley‐Liss, Inc.