Nefiracetam
Nefiracetam, a nootropic. Pyrrolidone (racetam-class) cognition enhancer, structurally an anilide of piracetam. Enhances acetylcholine release… Oral half-life 3.9 h.
Pyrrolidone (racetam-class) cognition enhancer, structurally an anilide of piracetam. Enhances acetylcholine release through modulation of L- and N-type voltage-gated calcium channels rather than through cholinesterase inhibition, and potentiates nicotinic and NMDA currents; mechanistically it groups with piracetam/aniracetam rather than with the SV2A-binding levetiracetam branch. Cleared almost entirely by hepatic oxidation — 5-hydroxylation by CYP3A4 is the principal human route — with under 10% of a dose excreted unchanged in urine.
PubChem CID 71157 (C14H18N2O2). PK: Fujimaki 1993 (PMID:8484264), healthy volunteers, single 200 mg oral dose — verbatim "tmax and t1/2 values of the metabolites (4.1-9.6 h and 7.8-21.9 h, respectively) were longer than those of I (1.6 h and 3.9 h respectively)", where I is nefiracetam itself. t½ 3.9 h is that point value; ka 1.52 /h is back-derived to the verbatim 1.6 h Tmax at ke = ln2/3.9, following the established Tmax-anchored ka convention. Cross-checks against the independent single/multiple-dose study Fujimaki 1992 (PMID:1360528): "declined monophasically after Cmax with half-lives of 3-5 h" and "Cmax within 2 h" both contain the stored values. VOLUME AND F DELIBERATELY ABSENT. A V/F of 37.5 L is derivable from the same abstract (Cmax 16.3 nmol/ml at 200 mg → 4.015 mg/L at MW 246.30; F·D/V = 4.015·e^(0.17773·1.6) = 5.336 mg/L; 200/5.336 = 37.5 L) and it cross-checks — ke·V/F = 111 mL/min, inside the "apparent clearance (CL) values were 94.4-140.3 mL min-1" of PMID:1360528. It is not stored because 37.5 L is 0.536 L/kg, within 7% of the solver default the 2026-09-08 sweep purged from 23 records, and because the derived quantity is V/F while no absolute bioavailability is published, so any stored pair would assert an F nobody measured. The defaults land within 4% of the observed peak, so omission costs nothing and claims nothing. Metabolism: Fujimaki 1996 (PMID:8879146) verbatim "5-OH-NEF formation by CYP3A4 is the principal metabolic pathway in humans" (human-P450-expressing microsomes). Dose range is the 200 mg three-times-daily regimen of PMID:1360528 and the 600 and 900 mg/day arms of the post-stroke apathy trial PMID:19622685, expressed per administration. Efficacy is NOT established: the Drugs review PMID:20166767 states "nefiracetam failed to improve cognition in post-stroke patients".
Pharmacokinetics
- Oral — t½ 3.9 h · ka 1.52 h⁻¹
Sources: PMID:8484264, PMID:1360528, PMID:8879146, PMID:19622685, PMID:20166767, PMID:15991988