Declopramide

Declopramide, also known as 3-chloroprocainamide or 3-CPA, is an N-substituted 4-aminobenzamide, structurally related to procainamide and metoclopramide. It exhibits multiple cellular effects with potential applications in oncology and anti-inflammatory contexts. Declopramide induces apoptosis in tumor cells by triggering cytochrome c release and caspase-9 activation, a process that can be inhibited by Bcl-2 overexpression. It also inhibits NF-kappaB activation by preventing the breakdown of IkappaBalpha and IkappaBbeta, and induces a G2/M cell cycle block. Furthermore, declopramide inhibits cell proliferation and causes massive cell vacuolization through V-ATPase-dependent ion trapping. Unlike metoclopramide, declopramide does not induce central nervous system (CNS) side effects at high doses and does not bind to dopamine D2 receptors, but it does bind to 5-hydroxytryptamine3 receptors. It has a rapid clearance, lower tissue concentration, and lower oral bioavailability compared to metoclopramide, but shows a higher tumor cell absorption rate. Its N-acetylated metabolite, N-acetyl-declopramide, also possesses significant antitumor activity.

Other names

3-chloroprocainamide