Dr Mariano, do you have an experience with NMDA antagonist ?

http://www.jaoa.org/cgi/content/full/106/6/358

Memantine: The Next Trend in Academic Performance Enhancement?
KEN S. OTA, OMS III; TINA GODWIN, OMS II

Western University of Health Sciences College of Osteopathic Medicine of the Pacific Pomona, Calif

To the Editor: Although memantine hydrochloride is currently known as the latest treatment for moderate-to-severe Alzheimer disease (AD),1 we entertain the idea that it might also come to be known as a memory enhancer among healthy high achievers.

The drug acts by noncompetitively binding to the N-methyl D-aspartate (NMDA) receptors of neurons in brain tissue to prevent overstimulation by glutamate. 2 When this excitatory neurotransmitter overactivates NMDA receptors in a tonic manner, an excessive influx of neurotoxic calcium ions follows. 2 The resultant excitotoxicity may play a role in the impairment of memory and cognition in AD. 3 Because memantine has a low-to-moderate affinity for NMDA receptors, it does not seem to block normal glutamate transmission; rather, it reduces abnormal neurotransmitter-mediated activation of the receptors, 4 thereby potentially reducing excitotoxic neuronal damage. This form of neuroprotection may explain the improved cognition in patients with AD reported in the literature. 5–7

Can transient low-level, nonpathologic, glutamate-mediated neuronal damage occur in the brains of normal individuals? And, if so, could memantine’s neuroprotective effect antagonize the damaging effects and enhance memory potential in these individuals? Future research should address these issues.

Memantine’s suggested neuroprotective effect 2,8 may also increase brain levels of the neuronal marker, N-acetyl aspartate (NAA). Because NAA is found primarily on neuronal axons in the brain, 9 perhaps the neuroprotective effect of memantine can be measured by quantifying the change in NAA concentrations in brain tissue via magnetic resonance spectroscopy. Magnetic resonance spectroscopy has demonstrated that patients with AD show a decline in NAA relative to normal controls. 10 The reduction in excitotoxicity via memantine’s mechanism of action may allow affected neurons to regain some level of physiologic functioning, such as growth of neuronal processes and synaptogenesis, which is fundamental to learning and memory formation 11 —a process that is damaged in AD. 2

Moreover, a direct relationship has been observed between NAA levels in the brain and intelligence. Healthy individuals with high levels of NAA appear to have higher scores on intelligence tests than healthy individuals with lower levels of this marker in brain tissue. 12 It may be possible that the higher levels of NAA indicate an increased presence of neuronal processes and their synapses.

The effects of drugs that have cognitive-enhancing potential have been studied in healthy individuals. Acetylcholinesterase inhibitors (some of which are used to treat AD), such as donepezil, huperzine , and physostigmine, have been shown to improve memory and cognitive tasks in normal subjects. 13–15 Another medication that enhances cognitive performance is methylphenidate, a drug commonly prescribed for attention deficit hyperactivity disorder (ADHD) but increasingly used by healthy university students nationwide as an academic performance–enhancing agent. 16 A recent national survey 17 reported that ADHD medications have much higher rates of abuse in colleges with higher admission standards. In light of all of the mentioned factors and the recent reports regarding the misuse of anabolic-androgenic steroids for the enhancement of athletic performance, 18,19 the misuse of memory-enhancing drugs to improve academic performance by some ambitious students may not be a far-fetched conjecture. The purpose of this letter is to raise a medically and ethically relevant question: If transient low-level, nonpathologic, glutamate-mediated neuronal damage can occur in normal brain tissue, and neuroprotection against this occurrence could promote neuroplastic processes such as synaptogenesis, could memantine be misused by students for academic performance-enhancement in the near future?