Evaluation of Pharmacological Profile of Meloxicam as an Anti-Inflammatory Agent, with Particular Reference to Its Relative Selectivity for Cyclooxygenase-2 Over Cyclooxygenase-1

Abstract

We studied the anti-inflammatory activity of meloxicam on rat carrageenin-induced pleurisy and its toxicity for rat gastric mucosa, relative to its in vitro inhibitory potency against partially purified cyclooxygenase (COX)-1 and COX-2 preparations in order to clarify the pharmacological profile of the compound as an anti-inflammatory agent. In rat carrageenin-induced pleurisy, the plasma exudation rate peaked at 5 h, at which time COX-2 was detectable in cells from the pleural exudate. Meloxicam and piroxicam (1 and 3 mg/kg) and NS-398 (3 mg/kg) showed almost equal anti-inflammatory potency against 5-hour pleurisy. A single oral administration of the compounds caused a dose-dependent increase in the number of rats with gastric mucosal erosion. The ED₅₀ value for meloxicam (5.92 mg/kg) was significantly higher than that for piroxicam (1.76 mg/kg), indicating that meloxicam is safer. Indometacin showed intermediate safety (2.59 mg/kg). In in vitro experiments, indometacin inhibited COX-1 about 1.7 times more potently than COX-2. NS-398 inhibited COX-2 with an IC50 of 0.32 µM, but never affected COX-1 activity, even at 100 µM. In the same assay system, meloxicam inhibited COX-2 about 12 times more selectively than COX-1. Piroxicam, however, inhibited both isoforms almost equally. These results indicate that meloxicam is a potent anti-inflammatory agent with low gastric toxicity. One reason for its in vivo pharmacological profile may be related to its relative selectivity for COX-2 over COX-1. Thus, meloxicam may belong to a group of COX-2 selective anti-inflammatory agents with a better safety profile than conventional COX-1 and COX-2 nonselective anti-inflammatory agents.

Expression of cyclooxygenase-2 in human esophageal squamous cell carcinomas

“…Similar results have been reported [43][44][45] . The significance of COX-2 likely varies between different classes of tumors.…”

Dissection of Metabolic, Vascular, and Nerve Conduction Interrelationships in Experimental Diabetic Neuropathy by Cyclooxygenase Inhibition and Acetyl-l-Carnitine Administration

“…The selective COX-2 inhibitor meloxicam (relative IC 50 , COX-2 vs. COX-1: 0.08 [41,42]) was given for 4 weeks (1 mg ⅐ kg -1 ⅐ day -1 in drinking water) to ND and STZ-D rats, with the dose adjusted in STZ-D animals to ensure equality of dosing. The initial study evaluated the effects of meloxicam on nerve metabolic end points, and a second study used expanded animal groups to explore potential effects of meloxicam on nerve electrophysiology and NBF.…”

Efficacy Assessment of Meloxicam, a Preferential Cyclooxygenase-2 Inhibitor, in Acute Coronary Syndromes Without ST-Segment Elevation

“…12 The group of COX-2 inhibitors includes meloxicam, which has potent anti-inflammatory activity and low gastric toxicity. 13,14 Studies show that meloxicam inhibits prostaglandin biosynthesis more potently at the site of inflammation than in the gastric mucosa or the kidney. 15 Although previous clinical studies with anti-inflammatory drugs did not demonstrate improved outcomes in patients with UA or myocardial infarction (MI), 16,17 we wished to assess the efficacy of the COX-2 inhibitor meloxicam in patients with acute coronary syndromes (ACS) without STsegment elevation.…”