Duloxetine Hydrochloride

Using a high‑throughput screen, the FDA‑approved serotonin‑norepinephrine reuptake inhibitor duloxetine was identified as an effective autophagy inhibitor at low‑micromolar concentrations. In young and aged mice subjected to photothrombotic stroke, duloxetine significantly reduced infarct size and improved locomotor performance, effects mirrored in transgenic mice lacking the autophagy gene Atg5 in excitatory neurons. Mechanistically, duloxetine inhibited TRPM2 ion channels. The authors conclude that early autophagy inhibition is neuroprotective in stroke and that duloxetine offers a clinically feasible means to achieve this.

Fig. 1 Study overview and in silico compounds selection based on drug-like and CNS-related properties. (Viotti A, et al., 2026)

Mesoporous silica nanoparticles (MSNs) synthesized by sol‑gel and solvothermal methods were loaded with duloxetine hydrochloride (DX). At pH 7.4, DX release reached 90%, but at acidic pH only 40%. TW60‑3DX MSNs showed sustained release over 140 hours following anomalous (non‑Fickian) diffusion (Peppas model n=0.45‑1, r²>0.9). The MSNs provide higher drug loading and pH‑responsive release, making them a promising carrier for acid‑labile drugs like duloxetine.

Fig. 2 Cumulative drug release pattern of TW60-1DX, TW60-2DX, and TW40-3DX. (Ganesh M, et al., 2015)