Clinical evaluation of H1-receptor and H2-receptor antagonists for acute postoperative pain

The acute analgesic activity of an H1-histamine antagonist, terfenadine 60 mg, and an H2-histamine antagonist, ranitidine 150 mg, were compared with ibuprofen 600 mg and placebo in a double-blind, placebo-controlled, parallel-group study. Treatments were administered to a total of 127 patients 1 hour before oral surgery. Analgesia was assessed every 30 minutes for 240 minutes after surgery. Analgesic efficacy was compared using the following standard pain intensity scales: visual analog scale, category, graphic rating, and global evaluation. Ibuprofen was significantly better than all other treatments for all measures of analgesic activity. The effects of terfenadine and ranitidine were similar to placebo. These data indicate that pretreatments with a single dose of a histamine receptor antagonist specific for either the H1- or H2-receptor does not produce analgesia in an oral surgery model of acute pain with overall assay sensitivity, suggesting that antihistamines that act primarily at peripheral sites are devoid of analgesic activity. These data contrast with other studies that have demonstrated analgesia using centrally acting antihistamines such as hydroxyzine, phenyltoloxamine, or orphenadrine.
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