Can we teach old drugs new tricks?-Repurposing of neuropharmacological drugs for inflammatory skin diseases

Exp Dermatol. 2019 Sep;28(9):1002-1009. doi: 10.1111/exd.13987. Epub 2019 Jul 4.

Abstract

Despite the "hype" for monoclonal antibodies, the so-called biologics, which added significant value to the therapeutic armamentarium of dermatologists and improved the life of many patients, but may exhibit significant adverse effects, the vast majority of dermatological patients suffering from atopic dermatitis or psoriasis is still treated topically. Thus, there is a huge need for locally applied, locally acting drugs for inflammatory skin diseases with better risk-benefit profiles compared to topical corticosteroids or calcineurin inhibitors. Drug repositioning is a complex process, but offers advantages, in particular for indications with lower revenues. In this viewpoint, the neuroendocrine system of the skin is described as an attractive drug target because it contributes significantly to neutralizing external noxious agents prior to inducing immune or vascular changes leading to the clinical signs of skin inflammation, for example, itch and erythema. In addition, epidermis and dermis are accessible for topically applied products which may act locally without pharmacodynamically relevant systemic exposure limiting adverse events. Moreover, since numerous drugs have been evaluated for various CNS diseases, some failed and some approved, this resource should be exploited for repurposing as anti-inflammatory drugs for topical application, for example, cannabidiol, fingolimod or asimadoline. Finally, a screening algorithm is shared which gives direct evidence of links between drug and inflammatory skin diseases.

Keywords: acne; dermatitis; drug screening; neuroendocrine; repositioning.

MeSH terms

  • Acetamides / pharmacology
  • Acetamides / therapeutic use
  • Administration, Cutaneous
  • Algorithms
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cannabidiol / pharmacology
  • Cannabidiol / therapeutic use
  • Dermatitis / drug therapy*
  • Dermatologic Agents / administration & dosage
  • Dermatologic Agents / pharmacology
  • Dermatologic Agents / therapeutic use*
  • Drug Evaluation, Preclinical / methods
  • Drug Repositioning*
  • Fingolimod Hydrochloride / pharmacology
  • Fingolimod Hydrochloride / therapeutic use
  • Humans
  • Keratinocytes / drug effects
  • Minoxidil / pharmacology
  • Minoxidil / therapeutic use
  • Neurosecretory Systems / physiology
  • Pyrrolidines / pharmacology
  • Pyrrolidines / therapeutic use
  • Sebaceous Glands / drug effects
  • Skin / drug effects
  • Skin / immunology

Substances

  • Acetamides
  • Anti-Inflammatory Agents
  • Dermatologic Agents
  • Pyrrolidines
  • Cannabidiol
  • Minoxidil
  • asimadoline
  • Fingolimod Hydrochloride