This paper reviews the clinical information on antihistaminic agents as analgesics and as analgesic adjuvants. The evidence indicates a direct analgesic effect of various antihistaminics. In clinical studies, diphenhydramine, hydroxyzine, orphenadrine and pyrilamine have been shown to produce analgesia as simple entities but chlorpheniramine has not and results with phenyltoloxamine have been equivocal when tested alone. Analgesic adjuvant effects of several antihistaminics have been reported. Clinically, orphenadrine and phenyltoloxamine have shown adjuvant effects with acetaminophen and aspirin. The mechanism of action remains speculative. The most recent trends in the classification of histamine receptors and how these receptors may interact with pain modulation are also considered.

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Salicylates, especially salsalate, appear to be a promising treatment option for prevention or treatment of diabetes by lowering glucose levels. More extensive studies are needed to confirm the mechanisms involved and whether the effects are sustainable with continued administration of these agents. Further studies are warranted.