
Biochemistry: Can Non‐steroidal Anti‐inflammatory Drugs Act as Metalloproteinase Modulators? An In‐vitro Study of Inhibition of Collagenase Activity
Author(s) -
BARRACCHINI ANNALISA,
FRANCESCHINI NICOLA,
AMICOSANTE GIANFRANCO,
ORATORE ARDUINO,
MINISOLA GIOVANNI,
PANTALEONI GIANCARLO,
GIULIO ANTONIO
Publication year - 1998
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/j.2042-7158.1998.tb03369.x
Subject(s) - collagenase , pharmacology , chemistry , nimesulide , meloxicam , piroxicam , in vitro , gold sodium thiomalate , sulindac , enzyme , biochemistry , medicine , rheumatoid arthritis , alternative medicine , pathology , nonsteroidal
The in‐vitro effects of some non‐steroidal anti‐inflammatory drugs and some analgesic drugs on collagenase activity were studied by use of a self‐quenched fluorogenic esapeptide as substrate. The increased fluorescence signal arising as a result of peptide cleavage by collagenase was recorded and related to the inhibitory potency of the drugs. The effective concentrations in collagenase modulation were also correlated with the levels of the drugs in the plasma and synovial fluids of patients receiving therapeutic doses. Six of the tested drugs, nimesulide, piroxicam, tolmetin, meloxicam, sulindac and sodium meclofenamate, inhibited enzyme activity with IC50 values (concentrations resulting in 50% inhibition) ranging from 1.9 to 28.2 μM and K i (apparent inhibition constant) ranging from 0.83 to 21.8 μM. Much of the activity was restored after dialysis of the enzyme‐drug complex, demonstrating the reversibility of the effect. Although these results indicate that some anti‐inflammatory drugs could modulate enzymatic activity involved in the degradation of the extracellular matrix, their possible pharmacological involvement as collagenase inhibitors in collagen degradative diseases remains to be assessed by clinical studies.