Doxepin affects acetylcholine induced cutaneous reactions in atopic eczema

Background Atopic eczema (AE) is a chronic inflammatory skin disease with s trong itching as the prominent symptom. The pathology of itch is still in d iscussion, but acetylcholine (ACH) seems to be a relevant pruritogenic medi ator in AE. Since efficient benefit on pruritus and excoriations has been d emonstrated with tricyclic agents, we investigated how the topical treatmen t with doxepin (5%, Boehringer Standard, Mannheim, Germany), a tricyclic co mpound with anticholinergic properties, may influence ACH induced itch and cutaneous sensations (erythema, wheal, axonreflex flare). Methods: Eleven p atients with AE were included in this double blind study. For 3 days we app lied doxepin cream to a defined area on the volar forearm and basic ointmen t to the other side 4 times daily. On day 4, ACH and sodium chloride were i .c, injected into the pretreated arms. Vasoreactions and cutaneous sensatio ns were measured similar to studies described in previous publications from our group. Results. Doxepin treatment over 3 days reduced ACH provoked fla re size more than 53% (P < 0.005) and wheal size about 48% (P < 0.005) wher eas the maximal antipruritic effect was similar to the basic therapy. The i tch intensity, which is expressed as the mean AUC value, was rated at 6.12 arbitrary units after the neutral cream application and 5.9 arbitrary units after doxepin. Conclusions. The clinical and experimental effectiveness of doxepin as an antipruritic drug has been known for years. However, studies focusing on ACH as a pruritogenic mediator have not been performed. The du ration of the doxepin application in our study seems to be appropriate sinc e flare and wheal development were diminished. The reason why doxepin did n ot develop more antipruritic action compared to the vehicle cream may be du e to the fact that the doxepin free cream already possessed an antipruritic action in this experimental study design. This is probably caused by rehyd rating and moisturizing effects.