Nefiracetam – 60 κάψουλες 100mg

Nefiracetam 100 mg — 60 ερευνητικές κάψουλες από του στόματος. Nefiracetam (DM-9384) is one of the most clinically advanced members of the entire racetam class — the subject of multi-thousκαι-patient Phase II/III trials in post-stroke depression, post-stroke apathy και Alzheimer’s disease at Mitsubishi Tanabe Pharma in Japan. Mechanistically, Nefiracetam pairs the canonical racetam cholinergic και glutamatergic profile with two distinctive additional activities: GABA-A positive modulation that produces an anxiolytic phenotype not seen in piracetam or aniracetam, και 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.

Επισκόπηση έρευνας

Nefiracetam (DM-9384) is a 2-pyrrolidinone-derivative nootropic developed by Daiichi (later Mitsubishi Tanabe Pharma) in Japan in the 1980s, και 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 και post-stroke apathy, Nefiracetam produced significant separation from placebo on Hamilton Depression και 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 και acetylcholine release) και pro-glutamatergic profile (NMDA-receptor potentiation σε 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) και 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 και 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-thousκαι patient-years of clinical exposure.

Κύριοι τομείς έρευνας

• Post-stroke depression και apathy research — the only racetam with Phase II/III RCT evidence in these indications, και one of the few molecules σεny class with a documented signal on post-stroke apathy [1,2].
• Cholinergic και glutamatergic pharmacology — enhancement of high-affinity choline uptake, ACh release και NMDA-receptor potentiation — the canonical racetam profile [1,3].
• Θετική αλλοστερική ρύθμιση GABA-A — ο αγχολυτικός φαινότυπος διακρίνει τη νεφιρακετάμη από τις προηγούμενες ρακετάμες (πιρακετάμη, ανιρακετάμη) [2].
• Φαρμακολογία διαύλων ασβεστίου τύπου L τασεοελεγχόμενων — ο μοναδικός μηχανισμός διαύλων ασβεστίου εντός της κατηγορίας των ρακεταμών, με εφαρμογές στην έρευνα συναπτικής πλαστικότητας μετά από ισχαιμία [3].
• Έρευνα νόσου Alzheimer — έχει προχωρήσει σε Φάση II στη νόσο Alzheimer· χρήσιμο μόριο σύγκρισης έναντι νεότερων χημειοτύπων γνωστικής ενίσχυσης [1].

Βιβλιογραφία

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.