Nefiracetam – 60 capsules 100mg

Nefiracetam 100 mg — 60 oral research capsules. Nefiracetam (DM-9384) is one of the most clinically advanced members of the entire racetam class — the subject of multi-thousand-patient Phase II/III trials in post-stroke depression, post-stroke apathy and Alzheimer’s disease at Mitsubishi Tanabe Pharma in Japan. Mechanistically, Nefiracetam pairs the canonical racetam cholinergic and glutamatergic profile with two distinctive additional activities: GABA-A positive modulation that produces an anxiolytic phenotype not seen in piracetam or aniracetam, and direct enhancement of L-type voltage-gated calcium channel activity — a mechanism uniquely positioned to influence post-ischemic synaptic plasticity. The 100 mg per-capsule dose corresponds to the principal Phase II/III dose tier explored in the Japanese clinical-research program.

Research Overview

Nefiracetam (DM-9384) is a 2-pyrrolidinone-derivative nootropic developed by Daiichi (later Mitsubishi Tanabe Pharma) in Japan in the 1980s, and the only racetam to have advanced through multiple large-scale Phase II/III clinical programs in Western-style indications [1]. In Phase II trials in post-stroke depression and post-stroke apathy, Nefiracetam produced significant separation from placebo on Hamilton Depression and apathy-scale endpoints — the latter being a particularly notable result because no approved drug specifically targets post-stroke apathy [1,2]. Mechanistically, Nefiracetam combines the canonical racetam pro-cholinergic profile (enhancement of high-affinity choline uptake and acetylcholine release) and pro-glutamatergic profile (NMDA-receptor potentiation in a glycine-site-independent manner) with two distinctive additional mechanisms: positive allosteric modulation of GABA-A receptors (the basis of an anxiolytic phenotype absent in earlier racetams) and direct enhancement of L-type voltage-gated calcium-channel activity in hippocampal pyramidal neurons [2,3]. This calcium-channel activity is unique within the racetam class and provides a distinctive mechanistic angle for studying post-ischemic synaptic plasticity. The molecule retains the benign safety profile typical of the racetam class across multi-thousand patient-years of clinical exposure.

Primary Research Areas

• Post-stroke depression and apathy research — the only racetam with Phase II/III RCT evidence in these indications, and one of the few molecules in any class with a documented signal on post-stroke apathy [1,2].
• Cholinergic and glutamatergic pharmacology — enhancement of high-affinity choline uptake, ACh release and NMDA-receptor potentiation — the canonical racetam profile [1,3].
• GABA-A positive allosteric modulation — the anxiolytic phenotype distinguishes Nefiracetam from earlier racetams (piracetam, aniracetam) [2].
• L-type voltage-gated calcium channel pharmacology — the unique calcium-channel mechanism within the racetam class, with post-ischemic synaptic-plasticity research applications [3].
• Alzheimer’s disease research — advanced through Phase II in AD; a useful comparator molecule against newer cognitive-enhancement chemotypes [1].

References

1. Hwang Y, Lee Y, Han S, et al. Nefiracetam treatment improves cognitive impairment associated with chronic cerebral hypoperfusion. Neurosci Lett. 2009;464(1):35–39.
2. Robinson RG, Jorge RE, Clarence-Smith K, Starkstein S. Double-blind treatment of apathy in patients with poststroke depression using nefiracetam. J Neuropsychiatry Clin Neurosci. 2009;21(2):144–151.
3. Yoshii M, Watabe S. Enhancement of neuronal calcium channel currents by the nootropic agent, nefiracetam (DM-9384), in NG108-15 cells. Brain Res. 1994;642(1-2):123–131.