Retinoic acid metabolism blocking agents (RAMBAs): a new paradigm in the treatment of hyperkeratotic disorders

Abstract

Synthetic vitamin A derivatives, retinoids,have long been the mainstay of treatment for several disorders of keratinization, notably the ichthyoses and severe acne. Some forms of psoriasis also respond well. Their considerable power comes at a price. They have dose-limiting side effects and can be highly teratogenic, limiting their use in women of childbearing age.Thus, retinoids are used less often than their potential would warrant. However, the recent development of compounds that block the catabolism of endogenous vitamin A, called Retinioic Acid Metabolism Blocking Agents or RAMBAs, offers new possibilities. With these drugs, retinoid effects with less side effects and a reduction of the post-treatment teratogenicity period due to their favourable pharmacokinetic profile might be expected. In this review, we discuss how retinoids work, how they are metabolized and how RAMBAs influence this process. We also review the presently available data from clinical trials with RAMBAs.