N-acetylserotonin, melatonin and their derivatives improve cognition and protect against beta-amyloid-induced neurotoxicity.
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.
Bachurin
S
S
Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Russia.
Oxenkrug
G
G
Lermontova
N
N
Afanasiev
A
A
Beznosko
B
B
Vankin
G
G
Shevtzova
E
E
Mukhina
T
T
Serkova
T
T
D000544:Alzheimer Disease / Q000139:chemically induced; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001388:Aziridines; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects; D002794:Choline / Q000031:analogs & derivatives; D003071:Cognition / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D009466:Neuromuscular Blocking Agents; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D001388:Aziridines; D009466:Neuromuscular Blocking Agents; D018697:Nootropic Agents; D012701:Serotonin; C044894:ethylcholine aziridinium; D008550:Melatonin; D002794:Choline; C006389:N-acetylserotonin