New evidence of H1-receptor independent COX-2 inhibition by fexofenadine HCl in vitro.
OBJECTIVE
Fexofenadine HCl (FEX) has previously been shown to have anti-inflammatory properties in relieving nasal congestion in allergic rhinitis. The objective of this study was to further elucidate the mechanism of action behind the anti-inflammatory properties of FEX in addition to its H(1)-receptor antagonism.


METHODS
The effects of two antihistamines, FEX and loratadine (LOR), were investigated on cyclooxygenase (COX)-1 and -2 enzymes in vitro. FEX (10(-9)-10(-3) mol/l) and LOR (10(-9)-10(-4) mol/l) were incubated with arachidonic acid in a COX screening assay with either ovine COX-1 or COX-2 or human COX-2. COX-2 enzyme inhibitory activity for the antihistamines was compared with the known selective COX-2 inhibitor DuP-679.


RESULTS
High concentrations of FEX (10(-3) mol/l) significantly inhibited arachidonic acid-mediated ovine COX-1 activity, but low concentrations had no effect. Low concentrations of FEX (10(-8) mol/l) inhibited ovine COX-2 activity, and this inhibition decreased with increasing concentrations. The inhibition of COX-2 activity by FEX was similar to that seen with the selective COX-2 inhibitor, DuP-679. Conversely, LOR inhibited COX-1 activity at low concentrations (10(-8) mol/l), but had little inhibitory effect on COX-1 at high concentrations. LOR (10(-5) mol/l) markedly stimulated COX-2 activity.


CONCLUSIONS
FEX showed selective arachidonic acid-mediated COX-2 inhibitory enzyme activity, which differed markedly from the COX inhibitory enzyme activity of LOR. This selective COX-2 inhibitor activity by FEX may contribute to its anti-inflammatory properties in relieving nasal congestion in allergic rhinitis.
Juergens
Uwe R
UR
Department of Pneumology, Medical Outpatient Clinic, Bonn University Hospital, Bonn, Germany. uwejuergens@t-online.de
Gillissen
Adrian
A
Uen
Sakir
S
Racké
Kurt
K
Stöber
Meinolf
M
Darlath
Wilfried
W
Vetter
Hans
H
D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D051545:Cyclooxygenase 1 / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000737:chemistry*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D012756:Sheep; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D006634:Histamine H1 Antagonists; D016718:Arachidonic Acid; D016593:Terfenadine; C093230:fexofenadine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2