Nefiracetam's cytoprotective actions are mediated by enhancement of GABAergic, cholinergic, and monoaminergic neuronal systems. It has been shown to effectively treat apathy and improve motivation in post-stroke patients. It has been shown to exhibit antiamnesia effects for the Alzheimer's type and cerebrovascular type of dementia. In addition, it has also been shown to have antiamnesia effects against a wide variety of memory impairing substances, including: ethanol, chlorodiazepoxide (Librium), scopolamine, bicuculline, picrotoxin, and cycloheximide.
Studies of long term consumption of nefiracetam in humans and primates have shown it to have no toxicity. However, animals which metabolize nefiracetam differently from humans and primates are at risk for renal and testicular toxicity. Dogs especially are particularly sensitive, which has been shown to be caused by a specific metabolite, M-18. Higher doses than those in dogs were needed to cause testicular toxicity in rats, although no toxicity was seen in monkeys. Additionally, there has been no evidence of toxicity during clinical trials.
^Robinson RG, Jorge RE, Clarence-Smith K, Starkstein S (2009). "Double-blind treatment of apathy in patients with poststroke depression using nefiracetam". The Journal of Neuropsychiatry and Clinical Neurosciences21 (2): 144–51. doi:10.1176/appi.neuropsych.21.2.144. PMID19622685.
^Robinson RG, Jorge RE, Clarence-Smith K (2008). "Double-blind randomized treatment of poststroke depression using nefiracetam". The Journal of Neuropsychiatry and Clinical Neurosciences20 (2): 178–84. doi:10.1176/appi.neuropsych.20.2.178. PMID18451188.
^Hiramatsu M, Shiotani T, Kameyama T, Nabeshima T. (Feb 1997). "Effects of nefiracetam on amnesia animal models with neuronal dysfunctions". Behavioural Brain Research. 83 1-2: 107–115.
^ abM Murasaki, M Inami, J Ishigooka, H Watanabe, M Utsumi, T Matsumoto et al. (1994). "Phase I study on DM-9384 (nefiracetam)". Jpn. Pharmacol. Ther.22: 3539–3587.
^ abE Otomo, K Kogure, S Hirai, F Goto, K Hasegawa, Y Tazaki et al. (1994). "Clinical evaluation of DM-9384 in the treatment of cerebrovascular disorders: early phase II study". Jpn. Pharmacol. Ther. (22): 3589–3624.
^Shimomura, K; Shimada, M; Hagiwara, M; Harada, S; Kato, M; Furuhama, K (2004). "Testicular toxicity induced in dogs by nefiracetam, a neutrotransmission enhancer". Reproductive toxicology (Elmsford, N.Y.)18 (3): 423–30. doi:10.1016/j.reprotox.2004.01.008. PMID15082078.
^Goto, Koichi; Ishii, Yoshikazu; Jindo, Toshimasa; Furuhama, Kazuhisa (3 March 2003). "Effect of Nefiracetam, a Neurotransmission Enhancer, on Primary Uroepithelial Cells of the Canine Urinary Bladder". Toxicological Sciences1 (72): 164–70. doi:10.1093/toxsci/kfg010. PMID12604846.|accessdate= requires |url= (help)