Biochemistry and biophysics reports · 2026
Therapeutic potential of CMPP, a novel maleimide derivative, in a reserpine-induced mouse model of pain-depression dyad.
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Alzoubi Lorca, Bsieso Yousra, Gammoh Omar, Aljabali Alaa A A, Salameh Bader A, Alqudah Abdelrahim, Qnais Esam, Al-Malkawi Ahmad M, Abu-Safieh Kayed
Аннотация
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.
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.