Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig...

Area of Science:

• Pharmacology
• Urology
• Gastroenterology

Background:

• Non-steroidal anti-inflammatory drugs (NSAIDs) are first-line treatments for renal colic, primarily acting via prostaglandin synthesis inhibition.
• The spasmolytic effects of NSAIDs on ureteral smooth muscle contractions are not well-understood, and effective ureteral spasmolytics are lacking.

Purpose of the Study:

• To investigate the influence of diclofenac (a non-selective COX inhibitor) and NS-398 (a selective COX-2 inhibitor) on induced contractions of the pig ureter.
• To assess the potential spasmolytic properties of NSAIDs in the context of renal colic treatment.

Main Methods:

• Isolated pig ureter preparations were used to study agonist-induced contractions (serotonin, norepinephrine, neurokinin A).
• The effects of varying concentrations of diclofenac and NS-398 on these contractions were measured.
• Reversibility of inhibition and the effect of prostaglandin F2alpha were also examined.

Main Results:

• Diclofenac and NS-398 demonstrated concentration-dependent inhibition of serotonin, norepinephrine, and neurokinin A-induced ureteral contractions.
• Neurokinin A-induced contractions were more sensitive to diclofenac inhibition than amine-induced contractions.
• Inhibition ranged from 25% to 96%, was fully reversible, and not reversed by prostaglandin F2alpha.

Conclusions:

• Diclofenac and NS-398 exhibit significant, reversible spasmolytic effects on the isolated porcine ureter.
• These findings suggest NSAIDs may offer additional benefits beyond pain relief and reduced diuresis in renal colic management.
• Selective COX-2 inhibitors show potential as spasmolytic agents for ureteral conditions with potentially fewer side effects.