Fonturacetam (phenylpiracetam, phenotropil, carphedon) is a phenylated analog of piracetam, synthesized in 1983 at the Institute of Biomedical Problems RAS under V. I. Akhapkina for maintaining psychophysiological performance in cosmonauts.
Mechanism of Action
Atypical dopamine reuptake inhibitor. DAT IC₅₀ ≈ 5.8 μM — comparable to modafinil (~4–5 μM); approximately 2-fold weaker than CE-123 (IC₅₀ 2.76 μM) and mesocarb. The atypical binding profile (similar to modafinil, mesocarb, solriamfetol) underlies the absence of cocaine-like abuse potential. The R-isomer shows 11-fold lower affinity for NET than DAT — providing a moderate adrenergic component without pronounced tachycardia. Weak modulator of α4β2 nicotinic acetylcholine receptors (IC₅₀ = 5.86 μM; nicotine ~1–10 nM, i.e. 100–500x more potent). As a racetam, also acts as an AMPA receptor potentiator.
Preclinical Data
Antiamnestic activity (scopolamine-induced amnesia model in rats): fonturacetam fully reverses passive avoidance deficits and partially normalizes scopolamine-induced receptor density changes — increases depressed striatal D1 receptor density, normalizes compensatorily elevated cortical nAChR and hippocampal NMDA receptor densities, and restores cortical benzodiazepine receptor levels. Antidepressant effect of R-isomer in forced swim test. Neuroprotection in ischemic and gravitational injury models. Reversal of diazepam sedation (benzodiazepine receptor antagonism). Anticonvulsant properties.
BIOLABCHEMICALS