Evaluation of pharmacological profile of meloxicam as an anti-inflammatory agent, with particular reference to its relative selectivity for cyclooxygenase-2 over cyclooxygenase-1

Pharmacology. 1997 Jul;55(1):44-53. doi: 10.1159/000139511.

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 microM, but never affected COX-1 activity, even at 100 microM. 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.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Carrageenan / administration & dosage
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Cyclooxygenase Inhibitors / therapeutic use
  • Dose-Response Relationship, Drug
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / pathology
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Indomethacin / toxicity
  • Isoenzymes / isolation & purification
  • Isoenzymes / metabolism*
  • Male
  • Meloxicam
  • Membrane Proteins
  • Nitrobenzenes / pharmacology
  • Nitrobenzenes / toxicity
  • Piroxicam / pharmacology
  • Piroxicam / toxicity
  • Pleurisy / chemically induced
  • Pleurisy / drug therapy
  • Prostaglandin-Endoperoxide Synthases / isolation & purification
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Rats
  • Rats, Wistar
  • Sulfonamides / pharmacology
  • Sulfonamides / toxicity
  • Therapeutic Equivalency
  • Thiazines / pharmacology*
  • Thiazines / therapeutic use
  • Thiazines / toxicity
  • Thiazoles / pharmacology*
  • Thiazoles / therapeutic use
  • Thiazoles / toxicity

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Nitrobenzenes
  • Sulfonamides
  • Thiazines
  • Thiazoles
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Piroxicam
  • Carrageenan
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, rat
  • Meloxicam
  • Indomethacin