Managing severe, chronic, debilitating pain has had limited therapeutic options, with most patients being unresponsive to conventional analgesic therapy. The approval of ziconotide, a peptide derived from the venom of the marine cone snail, validated antagonism of neuronal type (N-type) voltage-gated calcium channels (Cav2.2 channels) as an effective therapeutic target for this type of pain. Abbadie et al. describe the substituted N-triazole oxindole (TROX-1) as an orally administered state-dependent Cav2 calcium channel blocker that demonstrates analgesic activity in models of chronic inflammatory, osteoarthritic, and neurological pain, with similar efficacy to nonsteroidal anti-inflammatory agents, pregabalin, and duloxetine. The authors demonstrated that the analgesic activity of TROX-1 is primarily derived from state-dependent blockage of the Cav2.2 N-type calcium channels and, unlike ziconotide, which is a state-independent Cav2 blocker, TROX-1 produced no observable changes in motor coordination, cardiovascular function, or hemodynamic parameters. These studies support the notion that an orally administered, state-dependent Cav2 blocker such as TROX-1 may have therapeutic utility in the treatment of chronic, severe pain in the clinic.
See article at J Pharmacol Exp Ther 2010, 334:545–555.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics