Investigational drugs for pruritus

Chronic pruritus (CP), defined as itch lasting for > 6 weeks, is a burdensome symptom of several different diseases, dermatological and systemic, with a high negative impact on the quality of life of patients. Given the manifold aetiologies of CP, therapy is often difficult. In recent years, however, novel substances have been developed for treatment of certain CP entities and identified targets.

In this review, the authors present a survey of targets currently believed to be promising (H4R, IL-31, MOR, KOR, GRPR, NGF, NK-1R, TRP channels) and related investigational drugs that are in the preclinical or clinical stage of development. Some substances have already undergone clinical testing, but only one of them (nalfurafine) has been licensed so far. Many of them are most likely to exert their effects on the skin and interfere there with the cutaneous neurobiology of CP.

Currently, the most promising candidates for new therapeutic agents in CP are neurokinin-1 receptor antagonists and substances targeting the kappa- or mu-opioid receptor, or both. They have the potential to target the neuronal pathway of CP and are thus of interest for several CP entities. The goal for the coming years is to validate these concepts and move forward in developing new drugs for the therapy of CP.