Groene D, Martus P, Heyer G
Department of Dermatology, University of Erlangen-Nuremberg, 91052 Erlangen, Germany.
Exp Dermatol. 2001 Apr;10(2):110-7. doi: 10.1034/j.1600-0625.2001.010002110.x.
Atopic eczema (AE) is a chronic inflammatory skin disease with strong itching as the prominent symptom. The pathology of itch is still in discussion, but acetylcholine (ACH) seems to be a relevant pruritogenic mediator in AE. Since efficient benefit on pruritus and excoriations has been demonstrated with tricyclic agents, we investigated how the topical treatment with doxepin (5%, Boehringer Standard, Mannheim, Germany), a tricyclic compound with anticholinergic properties, may influence ACH induced itch and cutaneous sensations (erythema, wheal, axonreflex flare).
Eleven patients with AE were included in this double blind study. For 3 days we applied doxepin cream to a defined area on the volar forearm and basic ointment 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 sensations were measured similar to studies described in previous publications from our group.
Doxepin treatment over 3 days reduced ACH provoked flare size more than 53% (P<0.005) and wheal size about 48% (P<0.005) whereas the maximal antipruritic effect was similiar to the basic therapy. The itch 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.
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 duration of the doxepin application in our study seems to be appropriate since flare and wheal development were diminished. The reason why doxepin did not develop more antipruritic action compared to the vehicle cream may be due to the fact that the doxepin free cream already possessed an antipruritic action in this experimental study design. This is probably caused by rehydrating and moisturizing effects.
特应性皮炎（AE）是一种慢性炎症性皮肤病，以强烈瘙痒为突出症状。瘙痒的病理机制仍在探讨中，但乙酰胆碱（ACH）似乎是AE中一种相关的致痒介质。由于三环类药物已被证明对瘙痒和皮肤破损有显著疗效，我们研究了具有抗胆碱能特性的三环化合物多塞平（5%，德国曼海姆勃林格标准品）局部治疗如何影响ACH诱导的瘙痒及皮肤感觉（红斑、风团、轴突反射性潮红）。
11例AE患者纳入本双盲研究。连续3天，我们将多塞平乳膏每日4次涂抹于掌侧前臂的特定区域，另一侧涂抹基础软膏。第4天，将ACH和氯化钠皮内注射到预处理过的手臂。血管反应和皮肤感觉的测量方法与我们小组之前发表的研究类似。
3天的多塞平治疗使ACH诱发的潮红面积减少超过53%（P<0.005），风团面积减少约48%（P<0.005），而最大止痒效果与基础治疗相似。以平均AUC值表示的瘙痒强度，在涂抹中性乳膏后为6.12任意单位，在涂抹多塞平后为5.9任意单位。
多塞平作为一种止痒药物的临床和实验有效性已为人所知多年。然而，尚未开展以ACH作为致痒介质的研究。在我们的研究中，多塞平的应用时间似乎是合适的，因为潮红和风团的发展有所减轻。与赋形剂乳膏相比，多塞平没有产生更强止痒作用的原因可能是在本实验研究设计中，不含多塞平的乳膏已经具有止痒作用。这可能是由补水和保湿作用引起的。
