Inhibition of Erythema Induced by Pro‐inflammatory Esters of 12‐Deoxyphorbol

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Abstract
The pro-inflammatory tigliane esters 12-deoxyphorbolphenylacetate (12-DOPPA) and 12-deoxyphorbolphenylacetate-20-acetate (12-DOPPAA) at a dose of 0.1 .mu.g induced erythema in the mouse ear. Observations of ear redness were made both 2 and 4 h after application. Indomethacin was only partly successful as an antagonist since 10% inhibition of 12-DOPPA and no inhibition of 12-DOPPAA induced erythema was produced 4 h after application. The free radical scavengers, phenol, thioanisole and sodium benzoate all produced < 30% inhibition of 12-DOPPA induced erythema and < 15% inhibition of 12-DOPPAA, but aminopyrine produced 70 and 25% inhibition of 12-DOPPA and 12-DOPPAA, respectively. The fact that free radical scavengers (with the exception of aminopyrine) and indomethacin failed to markedly change the mouse ear reaction to 12-deoxyphorbol esters, indicated that this erythema is not entirely mediated via cyclooxygenase products. Mepyramine and cyproheptadine failed to inhibit the erythema, but hydrocortisone produced a 55% inhibition of the 12-DOPPA and a 20% inhibition of the 12-DOPPAA reaction. The membrane stabilizing agents trifluoperazine, promethazine, imipramine and desmethylimipramine were the most successful compounds used in inhibiting both 12-DOPPA and 12-DOPPAA induced erythema. In addition propranolol, which inhibits stimulus activation of phospholipase A2, produced 70% and 55% inhibition of the reaction of mice ears to 12-DOPPA and 12-DOPPAA.