Nefiracetam Explained

Nefiracetam is a nootropic drug of the racetam family. Preliminary research suggests that it may possess certain antidementia properties in rats.^[1]

Effects

Nefiracetam's cytoprotective actions are mediated by enhancement of GABAergic, cholinergic, and monoaminergic neuronal systems. 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.^{[2] [3]} In addition, research in animal models suggests antiamnesic effects against a number of memory impairing substances, including: ethanol, chlorodiazepoxide, scopolamine, bicuculline, picrotoxin, and cycloheximide.^[4]

Pharmacology

Unlike other racetams, nefiracetam shows high affinity for the GABA_A receptor (IC₅₀) = 8.5 nM), where it is presumed to be an agonist.^{[5] [6]} It was able to potently inhibit 80% of muscimol binding to the GABA_A receptor, although it failed to displace the remaining 20% of specific muscimol binding. Nefiracetam is able to reverse the amnesia caused by the GABA_A receptor antagonists picrotoxin and bicuculline in mice, although it failed to prevent seizures induced by these drugs.

Concerns

Studies of long-term consumption of nefiracetam in humans and primates have shown it to have no toxicity.^{[7] [8]} However, animals which metabolize nefiracetam differently from humans and primates are at risk for renal and testicular^{[9] [10]} toxicity. Dogs especially are particularly sensitive, which has been shown to be caused by a specific metabolite, M-18.^[11] 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.^{[7] [8]}

See also

• Racetams
• Guvacine
• Phenibut

Notes and References

1. Murphy KJ, Foley AG, O'connell AW, Regan CM . Chronic exposure of rats to cognition enhancing drugs produces a neuroplastic response identical to that obtained by complex environment rearing . Neuropsychopharmacology . 31 . 1 . 90–100 . January 2006 . 15988469 . 10.1038/sj.npp.1300810 . free .
2. Robinson RG, Jorge RE, Clarence-Smith K, Starkstein S . Double-blind treatment of apathy in patients with poststroke depression using nefiracetam . The Journal of Neuropsychiatry and Clinical Neurosciences . 21 . 2 . 144–151 . 2009 . 19622685 . 10.1176/appi.neuropsych.21.2.144 .
3. Robinson RG, Jorge RE, Clarence-Smith K . Double-blind randomized treatment of poststroke depression using nefiracetam . The Journal of Neuropsychiatry and Clinical Neurosciences . 20 . 2 . 178–184 . 2008 . 18451188 . 10.1176/appi.neuropsych.20.2.178 .
4. Hiramatsu M, Shiotani T, Kameyama T, Nabeshima T . Effects of nefiracetam on amnesia animal models with neuronal dysfunctions . Behavioural Brain Research . 83 . 1–2 . 107–115 . February 1997 . 9062668 . 10.1016/s0166-4328(97)86053-6 . 4045550 .
5. Gouliaev AH, Senning A . Piracetam and other structurally related nootropics . Brain Research. Brain Research Reviews . 19 . 2 . 180–222 . May 1994 . 8061686 . 10.1016/0165-0173(94)90011-6 . 18122566 .
6. Nabeshima T, Noda Y, Tohyama K, Itoh J, Kameyama T . Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions . European Journal of Pharmacology . 178 . 2 . 143–149 . March 1990 . 2328758 . 10.1016/0014-2999(90)90469-m .
7. Murasaki M, Inami M, Ishigooka J, Watanabe H, Utsumi M, Matsumoto T . Phase I study on DM-9384 (nefiracetam). Jpn. Pharmacol. Ther.. 1994. 22. 3539–3587. etal.
8. Otomo E, Kogure K, Hirai S, Goto F, Hasegawa K, Tazaki Y, etal . Clinical evaluation of DM-9384 in the treatment of cerebrovascular disorders: early phase II study. Jpn. Pharmacol. Ther.. 1994. 22. 3589–3624 .
9. Shimada M, Shikanai Y, Shimomura K, Harada S, Watanabe G, Taya K, Kato M, Furuhama K . 6 . Investigation of testicular toxicity of nefiracetam, a neurotransmission enhancer, in rats . Toxicology Letters . 143 . 3 . 307–315 . August 2003 . 12849691 . 10.1016/s0378-4274(03)00197-8 .
10. Shimomura K, Shimada M, Hagiwara M, Harada S, Kato M, Furuhama K . Testicular toxicity induced in dogs by nefiracetam, a neutrotransmission enhancer . Reproductive Toxicology . 18 . 3 . 423–430 . May 2004 . 15082078 . 10.1016/j.reprotox.2004.01.008 .
11. Goto K, Ishii Y, Jindo T, Furuhama K . Effect of nefiracetam, a neurotransmission enhancer, on primary uroepithelial cells of the canine urinary bladder . Toxicological Sciences . 72 . 1 . 164–170 . March 2003 . 12604846 . 10.1093/toxsci/kfg010 . free .