Parecoxib, a selective blocker of cyclooxygenase-2, directly inhibits neuronal delayed-rectifier K current, M-type K current and Na current.

Parecoxib, a prodrug of valdecoxib, is a selective inhibitor of cyclooxygenase-2 and widely used for traumatic and postoperative patients to avoid opioid-induced side effects. It is a potent analgesic and has a role in multimodal analgesic and enhanced recovery after surgery. Whether parecoxib exerts any actions on these types of ionic currents remains unclear. In this study, we investigated whether it exerts any effects on ion currents in differentiated NG108-15 neuronal cells. Cell exposure to parecoxib (1-30 μM) caused a reversible reduction in the amplitude of I with an IC value of 9.7 μM. The time course for the I inactivation in response to a long-lasting pulse was changed to the biexponential process during cell exposure to 3 μM parecoxib. Other agents known to inhibit the cyclooxygenase activity have minimal effects on I. Parecoxib enhanced the degree of excessive accumulative inhibition of I inactivation evoked by a train of brief repetitive stimuli. This compound suppressed the amplitude of M-type K current. It depressed the peak amplitude of voltage-gated Na current with no change in the current-voltage relationship of this current. However, it did not have any effect on hyperpolarization-activated cation current. No change in the expression level of K3.1 mRNA was detected in the presence of parecoxib. The effects of parecoxib on ion currents are direct and unrelated to its inhibition of the enzymatic activity of cyclooxygenase-2. The inhibition of these ion channels by parecoxib may partly contribute to the underlying mechanisms by which it affects neuronal function in vivo.