Optical isomers of a leukotriene b4 antagonist have differential effects on granulocyte diapedesis in the guinea pig dermis

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Abstract
Leukotriene B4 (LTB4) is a proinflammatory product of arachidonic acid metabolism that has been implicated in a number of inflammatory diseases. When injected intradermally into the guinea pig, LTB4 has been shown to elicit a dose‐dependent infiltration of granulocytes as assessed by the level of the neutrophil marker enzyme myeloperoxidase. SC‐41930 [7‐[3‐(4‐acetyl‐3‐methoxy‐2‐propylphenoxy)propoxy]‐3,4‐dihydro‐8‐propyl‐2H‐1‐benzopyran‐2‐carboxylic acid] is a potent LTB4 receptor antagonist. When compounds were coadministered along with LTB4 (35 ng) into the dermal site, racemic SC‐41930, (+)‐SC‐41930, and (–)‐SC‐41930 each inhibited granulocyte accumulation with ED50 values of 340 ± 30, 98 ± 5.7, and 1000 ± 142 ng, respectively; when given intravenously inhibited with ED50 values of 0.5 ± 0.06, 0.3 ± 0.04, and 1.4 ± 0.19 mg/kg, respectively; and when given intragastrically inhibited with ED50 values of 1.7 ± 0.20, 1.4 ± 0.23, and 3.0 ± 0.41 mg/kg, respectively.