Lacosamide reduces HDAC levels in the brain and improves memory: Potential for treatment of Alzheimer's disease.
Lacosamide, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of epilepsy. Some HDAC inhibitors have been proven effective for the treatment of memory disorders. The present investigation was designed to evaluate the effect of lacosamide on memory and brain HDAC levels. The effect on memory was evaluated in animals with scopolamine-induced amnesia using the elevated plus maze, object recognition test, and radial arm maze. The levels of acetylcholinesterase and HDAC in the cerebral cortex were evaluated. Lacosamide at doses of 10 and 30mg/kg significantly reduced the transfer latency in the elevated plus maze. Lacosamide at a dose of 30mg/kg significantly increased the time spent with a familiar object in the object recognition test at the 24h interval and decreased the time spent in the baited arm. Moreover, at this dose, the number of errors in the radial arm maze at 3 and 24h intervals was minimized and a reduction in the level of HDAC1, but not acetylcholinesterase, was observed in the cerebral cortex. These effects of lacosamide are equivalent to those of piracetam at a dose of 300mg/kg. These results suggest that lacosamide at a 30mg/kg dose improves disrupted memory, possibly by inhibiting HDAC, and could be used to treat amnesic symptoms of Alzheimer's disease.
Department of Pharmacology, JSPM's Jayawantrao Sawant College of Pharmacy and Research(1), Handewadi Road, Hadapsar, Pune 411028, India.
Shraddha R
SR
Bang
Department of Pharmacology, JSPM's Jayawantrao Sawant College of Pharmacy and Research(1), Handewadi Road, Hadapsar, Pune 411028, India. Electronic address: shirishkumar77@yahoo.com.
Shirishkumar D
SD
Ambavade
Department of Pharmacology, JSPM's Jayawantrao Sawant College of Pharmacy and Research(1), Handewadi Road, Hadapsar, Pune 411028, India.
Priti G
PG
Jagdale
Department of Pharmacology, JSPM's Jayawantrao Sawant College of Pharmacy and Research(1), Handewadi Road, Hadapsar, Pune 411028, India.
Prafulla P
PP
Adkar
Haffkine Biopharmaceutical Corporation Ltd., Pimpri, Pune 18, India.
Arun B
AB
Waghmare
Haffkine Biopharmaceutical Corporation Ltd., Pimpri, Pune 18, India.
Prashant D
PD
Ambavade
D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use; D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D006655:Histone Deacetylases / Q000378:metabolism*; D000078334:Lacosamide; D008568:Memory / Q000187:drug effects*; D051379:Mice; D051381:Rats; D017208:Rats, Wistar
D000081:Acetamides; D000078334:Lacosamide; D000110:Acetylcholinesterase; D006655:Histone Deacetylases
Acetylcholinesterase; HDAC; Lacosamide; Object recognition; Radial arm maze