Acute Effects of the Ampakine Farampator on Memory and Information Processing in Healthy Elderly Volunteers

Abstract

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, placebocontrolled, 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 T max 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.

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

“…Further, modulation of AMPA receptors has been evaluated in schizophrenia. Ampakines are compounds that interact with AMPA receptors to modulate synaptic activity by allosterically binding to the receptors to facilitate synaptic transmission (Wezenberg et al, 2007). Meta-analyses of studies using multiple adjunct therapies found that ampakines were ineffective in reducing the positive symptoms of schizophrenia (Goff et al, 2008;Tuominen et al, 2005;Tuominen et al, 2006).…”

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

“…The compound failed to have an effect in a phase II study simulating shift work (Wesensten et al, 2007). Another AMPA potentiator of the same class, farampator, showed acute effects on short term memory in a preliminary study in aged healthy human volunteers (Wezenberg et al, 2007).…”

Chronic intermittent hypoxia-induced deficits in synaptic plasticity and neurocognitive functions: a role for brain-derived neurotrophic factor

“…In addition, previous studies showed that regular ampakine administration would increase the expression of BDNF. Considering that ampakines can also cross the blood-brain barrier, are bioactive orally and improve cognitive function without obvious side effects, they are of great potential and in fact have been partially proved to be candidate for a range of neurological disability and disturbances, including Alzheimer's disease and Huntington's disease [58,[61][62][63] . We hypothesize that ampakines are beneficial to the neurocognitive problems found in OSA by its action in elevating endogenous BDNF level in the brain.…”