Nefiracetam

Some positive trial data in post-stroke apathy and cognition in Japan. Development was complicated by renal toxicity findings in dogs at high doses.

A rough internal score reflecting quantity, quality, and consistency of human evidence. Not a clinical recommendation.

Japanese Phase II trials showed improvement in post-stroke apathy and depression. Mechanism involves prolonged opening of L-type calcium channels and potentiation of nicotinic and GABAergic signaling. High-dose dog studies revealed renal tubular toxicity that limited clinical development.

• Multiple receptor targets including nicotinic, GABAergic, and calcium channels
• Improved post-stroke apathy in Japanese trials
• Enhances long-term potentiation in hippocampal models

Japanese trials used 600–900 mg/day. Nootropic users report 400–800 mg/day.

• GI discomfort
• Headache
• Potential nephrotoxicity at high doses

Renal toxicity observed in high-dose animal studies. Monitor kidney function with chronic use. Not widely approved.

The renal toxicity signal in animals, though at high doses, raised regulatory concerns and stalled development.

• Memory40
• Mood40
• Focus35