Declopramide

Declopramide (3-Chloroprocainamide) is an orally active, blood-brain barrier-permeable IκBβ/NF-κB inhibitor and chemosensitizer. Declopramide exhibits affinity for rabbit 5-HT₃ receptors (5-HT₃R) with a K_i value of 3.2 μM. Declopramide inhibits IκBβ degradation, blocks NFκB activation, and induces rapid apoptosis and DNA strand breaks in cancer cells. Declopramide enhances the cytotoxicity induced by Cisplatin (HY-17394) and is also metabolically converted to N-acetyl declopramide. Declopramide can be used in the research of tumors such as brain astrocytoma^[1][2][3]. In Vitro:Declopramide (250-1000 µM; 20 h) induces dose-dependent caspase-mediated early apoptosis in 70Z/3 mouse pre-B cells^[1].
Declopramide (250-1000 µM; 24 h) inhibits LPS-induced activation of NF-κB in 70Z/3 mouse pre-B cells^[1].
Declopramide inhibits the growth of HL60 and K562 leukemia cells in vitro, but its activity is weaker than that of its metabolite N-acetyl-declopramide^[2]. In Vivo:Declopramide (40 mg/kg; p.o.; administered 3 times) exerts a significant inhibitory effect on tumor growth in SCID mice bearing human T24 brain astrocytoma xenografts^[2].
Declopramide (25-200 mg/kg; i.m., p.o.; single dose) does not induce central nervous system-related sedative side effects in female Wistar-Furth rats^[3].
Declopramide (25 mg/kg; i.m., p.o.; single dose) distributes to the brain, spleen and tumor tissues in scid mice bearing H2981 xenografts^[3].