- Zhang, Y. et al. (2007) Pharmacol. Res. 56, 267.
- Alomone Labs Celecoxib blocks L-type CaV channel currents expressed in Xenopus oocytes.A. Time course of CaV1.2 (co-expressed with α2δ1 and β1 auxiliary subunits) currents, elicited by 100 ms voltage ramp from holding potential of -100 mV to +50 mV, delivered every 10 seconds. Application of 100 µM Celecoxib (#C-190) inhibits the current amplitude (period of application indicated by horizontal bar). B. Representative current traces before and during application of 100 µM Celecoxib as indicated.
Celecoxib is a non-steroidal anti-inflammatory drug (NSAID), which selectively inhibits the enzyme cyclo-oxygenase (COX)-2. NSAIDs are widely used to treat pain caused by inflammation-related complications, which are symptomatic in chronic or acute pathologies. Allegedly, NSAIDs prevent pain by inhibiting COX-1 and COX-2, which help to synthesize mediators of pain such as prostaglandins. While COX-1 is normally present in most healthy tissues, COX-2 is expressed only in damaged tissues and is mainly induced by inflammatory factors1.
The first generation of NSAIDs targeted both COXs. This led to unwanted gastrointestinal side effects due to the inhibition of COX-1. To minimize intervention with COX-1, selective COX-2 inhibitors (coxibs) were then developed. Celecoxib was the first clinically proven coxib. In vitro assays have shown that celecoxib inhibits COX-2 with an IC50 of 15 μmol/L. In addition, it efficiently blocks L-type Ca2+ channels (CaV1), but enhances the K+ voltage-gated channel KCNQ activity2,3.
Clinical trials have shown that celecoxib is a useful therapy for symptomatic pain relief, usually in various joint-related diseases such as osteoarthritis, rheumatoid arthritis, and Ankylosing Spondylitis. Unfortunately, it increases the risk of cardiovascular diseases, probably due to interfering with cardiac K+ channels1.
It was suggested that the drug might be implicated in other aspects of the COX-2 signaling pathway than the anti-inflammation effects4. Celecoxib is also being evaluated as a potential anti-cancer drug as it was found to induce apoptosis via specific pathways independent of COX-25.
Celecoxib (#C-190) is a highly pure, synthetic, and biologically active compound.