维甲酸类药物——哪些皮肤科适应症在不久的将来会从中受益?

Retinoids--which dermatological indications will benefit in the near future?

作者信息

Zouboulis C C

机构信息

Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Berlin, Germany.

出版信息

Skin Pharmacol Appl Skin Physiol. 2001 Sep-Oct;14(5):303-15. doi: 10.1159/000056361.

Abstract

Retinoids are compounds with pleiotropic functions and a relatively selective targeting of certain skin structures. They are vitamins, because retinol (vitamin A) is not synthesized in the body and must be derived from diet, but also hormones with intracrine activity, because retinol is transformed into molecules that bind to nuclear receptors, exhibit their activity, and are subsequently inactivated. Retinoids exert their effects on target cells by binding and activating nuclear retinoid receptors. Retinoid receptors bind their ligands in form of dimers. Heterodimers can be formed between two different retinoid receptor molecules but also between retinoid X receptors and the vitamin D receptor as well as the triiodothyronin receptor. This fact indicates complex interactions between retinoids and further hormonal signal transduction molecules. Interaction of retinoid receptors with transcriptional factors activated by other signal transduction mechanisms, e.g. AP-1, may provide dissociation of the retinoid effects. Retinoids can exhibit agonistic activity but also be neutral antagonists and inverse agonists. Topical and oral retinol, tretinoin, isotretinoin, and bexarotene, topical alitretinoin, retinaldehyde, motretinide, adapalene, tazarotene, and systemin acitretin compose the list of launched retinoids. Psoriasis and related disorders, congenital disorders of keratinization, acne, photoaging and hypovitaminosis A are classical approved indications of retinoid treatment, whereas cutaneous T-cell lymphoma, AIDS-associated Kaposi's sarcoma, acute promyelocytic leukemia and actinic lentigines were currently confirmed. In addition, retinoids have been successfully used in several other dermatoses, e.g. epithelial precanceroses and tumors, seborrhea, rosacea and acneiform dermatoses, lichen planus, eosinophilic folliculitis, condylomata accuminata, lichen sclerosus and atrophicus. Highly receptor selective molecules, retinoic acid receptor-beta-inducers, AP-1 complex antagonists, and inverse agonists will be probably lead the retinoid development in the near future. New, more effective and less toxic retinoids, alone or in combination with other drugs and new delivery systems may provide therapeutic solutions for benign and malignant proliferative skin diseases, such as psoriasis and non-melanoma tumors, cancer chemoprevention and differentiation therapy.

摘要

维甲酸类化合物具有多种功能,且对某些皮肤结构具有相对选择性靶向作用。它们属于维生素类,因为视黄醇(维生素A)无法在体内合成,必须从饮食中获取,但同时也是具有内分泌活性的激素,因为视黄醇会转化为与核受体结合的分子,发挥其活性,随后失活。维甲酸类化合物通过结合并激活核维甲酸受体对靶细胞发挥作用。维甲酸受体以二聚体形式结合其配体。异二聚体可在两种不同的维甲酸受体分子之间形成,也可在维甲酸X受体与维生素D受体以及三碘甲状腺原氨酸受体之间形成。这一事实表明维甲酸类化合物与其他激素信号转导分子之间存在复杂的相互作用。维甲酸受体与由其他信号转导机制(如AP-1)激活的转录因子相互作用,可能会导致维甲酸类化合物的效应解离。维甲酸类化合物可表现出激动活性,也可为中性拮抗剂和反向激动剂。外用和口服视黄醇、维甲酸、异维甲酸、贝沙罗汀,外用阿利维A酸、视黄醛、莫特维德、阿达帕林、他扎罗汀以及系统用阿维A构成了已上市维甲酸类药物的清单。银屑病及相关疾病、先天性角化异常、痤疮、光老化和维生素A缺乏症是维甲酸类治疗的经典获批适应证,而皮肤T细胞淋巴瘤、艾滋病相关的卡波西肉瘤、急性早幼粒细胞白血病和光化性雀斑目前也得到了证实。此外,维甲酸类化合物已成功用于其他多种皮肤病,如上皮癌前病变和肿瘤、脂溢性皮炎、玫瑰痤疮和痤疮样皮肤病、扁平苔藓、嗜酸性毛囊炎、尖锐湿疣以及硬化萎缩性苔藓。高受体选择性分子、维甲酸受体-β诱导剂、AP-1复合物拮抗剂和反向激动剂可能在不久的将来引领维甲酸类药物的发展。新型、更有效且毒性更低的维甲酸类药物,单独或与其他药物联合使用以及新的给药系统,可能为良性和恶性增殖性皮肤病,如银屑病和非黑色素瘤肿瘤、癌症化学预防和分化治疗提供治疗方案。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索