|  Neuropsychopharmacology.
2007 Jun;32(6):1272-83. Epub 2006 Nov 22.
Wezenberg E, Verkes RJ, Ruigt GS, Hulstijn W, Sabbe BG.
Department of Psychiatry (966), Radboud University Nijmegen
Medical Center, Nijmegen, The Netherlands.
Ampakines act as positive allosteric modulators of AMPA-type
glutamate receptors and facilitate hippocampal long-term potentiation
(LTP), a mechanism associated with memory storage and consolidation.
The present study investigated the acute effects of farampator,
1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information
processes in healthy elderly volunteers. A double-blind, placebo-controlled,
randomized, cross-over study was performed in 16 healthy, elderly
volunteers (eight male, eight female; mean age 66.1, SD 4.5 years).
All subjects received farampator (500 mg) and placebo. Testing
took place 1 h after drug intake, which was around Tmax for farampator.
Subjects performed tasks assessing episodic memory (wordlist learning
and picture memory), working and short-term memory (N-back, symbol
recall) and motor learning (maze task, pursuit rotor). Information
processing was assessed with a tangled lines task, the symbol
digit substitution test (SDST) and the continuous trail making
test (CTMT). Farampator (500 mg) unequivocally improved short-term
memory but appeared to impair episodic memory. Furthermore, it
tended to decrease the number of switching errors in the CTMT.
Drug-induced side effects (SEs) included headache, somnolence
and nausea. Subjects with SEs had significantly higher plasma
levels of farampator than subjects without SEs.
Additional analyses revealed that in the farampator condition
the group without SEs showed a significantly superior memory performance
relative to the group with SEs. The positive results on short-term
memory and the favorable trends in the trail making test (CTMT)
are interesting in view of the development of ampakines in the
treatment of Alzheimer's disease and schizophrenia. |
Ampakines
Therapeutic Uses