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Does the NMDA antagonist, Memantine that's used to prevent excitotoxicity in Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB) cause brain damage? I know that in rodents NMDA antagonists like ketamine and phencyclidine (PCP) cause a form of brain damage known as Olney's lesions. Despite Olney's lesions never being directly observed in primates like humans, permanent brain damage from chronic ketamine exposure has been observed in adolescent cynomolgus monkeys.1

Reference List

  1. Sun, Lin; Qi Li, Qing Li, Yuzhe Zhang, Dexiang Liu, Hong Jiang, Fang Pan, David T. Yew (2012). "Chronic ketamine exposure induces permanent impairment of brain functions in adolescent cynomolgus monkeys". Addiction Biology. doi:10.1111/adb.12004. PMID 23145560.
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Yes, it does cause lesions in rats, although I don't think it's been observed to do so in humans.

See: http://www.druglib.com/druginfo/namenda/description_pharmacology/

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  • $\begingroup$ Thanks, mate. That's helpful for me, of course in human studies would be more helpful but c'mon there's no such studies on the most widely-used NMDA antagonists like ketamine and PCP so I can hardly expect it for memantine -- a drug I had trouble finding evidence even in rodents. $\endgroup$
    – Josh Pinto
    Commented Feb 12, 2013 at 5:21
  • $\begingroup$ @BrentonHorne Apparently, memantine might cause hallucinations in humans (N=3): http://jnnp.bmj.com/content/78/5/546.1.short $\endgroup$
    – blep
    Commented Feb 12, 2013 at 7:04
  • $\begingroup$ What do you mean by N=3? $\endgroup$
    – Josh Pinto
    Commented Feb 12, 2013 at 7:55
  • $\begingroup$ N is commonly used to refer to sample size (at least among the biologists that I've spoken with). The article I linked is a case study of 3 individuals. My point is that this is an extremely small number of individuals with documented adverse affects to memantine. If you want to read the article, you can read the 1 page preview (as an image)...the whole article happens to be 1 page. $\endgroup$
    – blep
    Commented Feb 12, 2013 at 7:57
  • $\begingroup$ Ah, thanks, I assume you're talking about hallucinations because it makes the link between its NMDA antagonist activity and potential brain damage more clear by demonstrating that it has one of the effects characateristic of NMDA antagonists, i.e. hallucinations. $\endgroup$
    – Josh Pinto
    Commented Feb 12, 2013 at 8:10

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