ozagrel and histamine-phosphate

We studied the effect of a selective thromboxane-synthetase inhibitor, sodium (E)-3-[4-(1-imidazolymethyl)-phenyl]-2-propanoate) (OKY-046) on the late-phase response to antigen in ragweed-sensitized dogs. Skin biopsies were performed before and 1, 6, and 24 hours after ragweed injection. OKY-046 was infused (100 micrograms.kg-1.min) from 1 hour before until 6 hours after intracutaneous ragweed in five dogs. The early clinical response to ragweed (wheal at 20 minutes) was not changed by OKY-046. A late-phase response (induration at 6 hours) was not observed in any of the OKY-046-treated dogs but was present at 6 hours in 4/5 dogs without OKY-046. Typical mast cells responded similarly in both groups with progressive degranulation during 24 hours. Maximal degranulation of atypical mast cells was delayed to 6 hours with OKY-046, whereas these cells responded completely at 1 hour without OKY-046. The inflammatory response to ragweed followed the same pattern in both groups, but the numbers of each cell type were decreased with OKY-046. With OKY-046, the cutaneous response to histamine was not changed significantly from baseline at 6 hours but was increased (p less than 0.05) at 24 hours, whereas without OKY-046, histamine response was significantly increased at 6 hours (p less than 0.001) and 24 hours (p less than 0.01). We conclude that OKY-046 alters the antigen-induced response of atypical mast cells, the subsequent cellular and clinical late-phase response, and prevents the increase in histamine response.

Topics: Acrylates; Animals; Basophils; Biopsy; Dogs; Drug Evaluation, Preclinical; Histamine; Hypersensitivity; Mast Cells; Methacrylates; Pollen; Skin; Skin Tests; Thromboxane-A Synthase; Time Factors