@article {Kankaanranta1006, author = {H Kankaanranta and E Moilanen}, title = {Flufenamic and tolfenamic acids inhibit calcium influx in human polymorphonuclear leukocytes.}, volume = {47}, number = {5}, pages = {1006--1013}, year = {1995}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Fenamates, a subgroup of nonsteroidal anti-inflammatory drugs, inhibit several functions of human polymorphonuclear leukocytes (PMNs) in vitro, by a thus far unknown mechanism. To determine the mechanism behind this action, we studied the effects of two fenamates (flufenamic and tolfenamic acids) on Ca2+ metabolism in human PMNs. The two fenamates inhibited the increases in intracellular free calcium concentration induced by either the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine or the calcium ionophore A23187 in fura-2-labeled PMNs. This inhibition was concluded to be due to blocking of the cation influx, as evidenced by measurement of Mn2+ influx and the influx of radioactive calcium. In addition, the actions of flufenamic and tolfenamic acids were similar to those of an experimental blocker of nonselective cation channels (SK\&F 96365). The two other control compounds, an antagonist of voltage-dependent calcium channels (nifedipine) and an inhibitor of prostanoid synthesis (ketoprofen), were ineffective. In conclusion, inhibition of calcium influx in PMNs is introduced as a novel prostanoid-independent mode of action of two nonsteroidal anti-inflammatory drugs with fenamate structure, flufenamic and tolfenamic acids, which could explain their earlier documented inhibitory effects on PMN functions.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/47/5/1006}, eprint = {https://molpharm.aspetjournals.org/content/47/5/1006.full.pdf}, journal = {Molecular Pharmacology} }