Therapeutic potential of CMPP, a novel maleimide derivative, in a reserpine-induced mouse model of pain-depression dyad.

BACKGROUND

Pain and depression often coexist through shared mechanisms including monoamine depletion, oxidative stress, and inflammation. Multi-target therapies remain limited.

METHODS

The effects of 3-Chloro-4-morpholino-1-(4-(4-(pyridin-2-yl)piperazin-1-yl)but-2-yn-1-yl)-1H-pyrrole-2,5-dione (CMPP) were assessed in a reserpine-induced mouse model of pain-depression dyad. Mice received reserpine (0.5 mg/kg, s.c., 3 days) with CMPP (5, 10, or 20 mg/kg, p.o.) or gabapentin (10 mg/kg, p.o.) for behavioral evaluation. Based on the behavioral dose-screening results, the 10 mg/kg dose of CMPP was selected for subsequent biochemical analyses.

RESULTS

Reserpine reduced paw withdrawal thresholds in von Frey and PAM tests, increased immobility in the forced swim test, and prolonged escape latency in the Morris water maze. CMPP reversed these effects. Reserpine decreased brain GSH, increased TBARS, depleted serotonin and norepinephrine, elevated glutamate, and increased MAO-A activity. CMPP increased GSH, reduced TBARS, partially restored serotonin and norepinephrine, lowered glutamate, and inhibited MAO-A. It also suppressed serum TNF-α and IL-1β.

CONCLUSION

CMPP demonstrated antinociceptive, antidepressant-like, antioxidant, and anti-inflammatory effects, supporting its potential for treating pain-depression comorbidity.