After a single injection of cholinergic neurotoxin ethylcholine aziridinium (AF64A, 3 nmol intracerebroventricularly (i.c.v.)), rats failed to perform the tasks in the active avoidance (learning and retention paradigms) and water maze tests. N-Acetylserotonin (NAS), melatonin and their newly synthesized derivatives, CA-15 and CA-18, (0.3-3.0 mg/kg daily for 12-14 days) reversed the effect of AF64A in a dose-dependent manner with CA-18 being the most active. Melatonin and NAS caused sedation absent in CA-18-treated rats. The studied compounds (25-500 microM for 72 hr) protected against beta-amyloid peptide (beta AP) fragment 25-35-induced neurotoxicity in cerebellar granule cell culture. Our results suggest that neuroprotecting properties of these compounds might mediate their cognition-enhancing effects. The results obtained warrant the further search for the novel types of safe neuroprotectors among the synthetic NAS/melatonin derivatives.
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