Nefiracetam is a nootropic drug of the racetam family. Preliminary research suggests that it may possess certain antidementia properties in rats.[2]
Effects
Nefiracetam's cytoprotective actions are mediated by enhancement of GABAergic, cholinergic, and monoaminergic neuronal systems.[citation needed] Preliminary studies suggest that it improves apathy and motivation in post-stroke patients. It may also exhibit antiamnesia effects for the Alzheimer's type and cerebrovascular type of dementia.[3][4] In addition, research in animal models suggests antiamnesic effects against a number of memory impairing substances, including: ethanol, chlorodiazepoxide, scopolamine, bicuculline, picrotoxin, and cycloheximide.[5]
Pharmacology
Unlike other racetams, nefiracetam shows high affinity for the GABAA receptor (IC50) = 8.5 nM), where it is presumed to be an agonist.[6][7] It was able to potently inhibit 80% of muscimol binding to the GABAA receptor, although it failed to displace the remaining 20% of specific muscimol binding.[6][7] Nefiracetam is able to reverse the amnesia caused by the GABAA receptor antagonists picrotoxin and bicuculline in mice, although it failed to prevent seizures induced by these drugs.[7]
Concerns
Studies of long-term consumption of nefiracetam in humans and primates have shown it to have no toxicity.[8][9] However, animals which metabolize nefiracetam differently from humans and primates are at risk for renal and testicular[10][11] toxicity. Dogs especially are particularly sensitive, which has been shown to be caused by a specific metabolite, M-18 which isn't formed in humans.[12] 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.[8][9]
^Fujimaki Y, Sudo K, Hakusui H, Tachizawa H, Murasaki M (September 1992). "Single- and multiple-dose pharmacokinetics of nefiracetam, a new nootropic agent, in healthy volunteers". The Journal of Pharmacy and Pharmacology. 44 (9): 750–754. doi:10.1111/j.2042-7158.1992.tb05513.x. PMID1360528. S2CID25913554.
^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 Neurosciences. 21 (2): 144–151. 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 Neurosciences. 20 (2): 178–184. doi:10.1176/appi.neuropsych.20.2.178. PMID18451188.
^Hiramatsu M, Shiotani T, Kameyama T, Nabeshima T (February 1997). "Effects of nefiracetam on amnesia animal models with neuronal dysfunctions". Behavioural Brain Research. 83 (1–2): 107–115. doi:10.1016/s0166-4328(97)86053-6. PMID9062668. S2CID4045550.
^ abcNabeshima T, Noda Y, Tohyama K, Itoh J, Kameyama T (March 1990). "Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions". European Journal of Pharmacology. 178 (2): 143–149. doi:10.1016/0014-2999(90)90469-m. PMID2328758.
^ abMurasaki M, Inami M, Ishigooka J, Watanabe H, Utsumi M, Matsumoto T, et al. (1994). "Phase I study on DM-9384 (nefiracetam)". Jpn. Pharmacol. Ther. 22: 3539–3587.
^ abOtomo E, Kogure K, Hirai S, Goto F, Hasegawa K, Tazaki Y, et al. (1994). "Clinical evaluation of DM-9384 in the treatment of cerebrovascular disorders: early phase II study". Jpn. Pharmacol. Ther. (22): 3589–3624.
^Shimada M, Shikanai Y, Shimomura K, Harada S, Watanabe G, Taya K, et al. (August 2003). "Investigation of testicular toxicity of nefiracetam, a neurotransmission enhancer, in rats". Toxicology Letters. 143 (3): 307–315. doi:10.1016/s0378-4274(03)00197-8. PMID12849691.
^Shimomura K, Shimada M, Hagiwara M, Harada S, Kato M, Furuhama K (May 2004). "Testicular toxicity induced in dogs by nefiracetam, a neutrotransmission enhancer". Reproductive Toxicology. 18 (3): 423–430. doi:10.1016/j.reprotox.2004.01.008. PMID15082078.
