Serlopitant is a potent oral NK1 receptor antagonist that Menlo Therapeutics, Inc., licensed from Merck in 2012. It is highly selective for the human NK1 receptor and in both animal and human testing it has been well tolerated. The pharmacokinetics have been studied in animals and humans as well as the receptor binding allowing for rational dose selection for further trials. Beginning in 2005, Merck evaluated serlopitant in 13 Phase 1 studies and two Phase 2b studies, comprising over 900 subjects and patients. In the Phase 1 studies, single doses of 400 mg and multiple doses of 50 mg per day up to 28 days were generally well tolerated in healthy young males and in healthy elderly males and females (age ≤80 years). Merck also assessed serlopitant for safety and efficacy in a Phase 2 study in overactive bladder and in a Phase 2 study for alcohol dependence.
In 2012, Menlo Therapeutics licensed Serlopitant from Merck and redirected the development program to the treatment of pruritus.
ROLE OF SUBSTANCE P AND NK-1 RECEPTORS IN PRURITUS
Although pruritus is a frequent symptom of many dermatological and systemic conditions its pathophysiology is poorly understood. Pruritus is a cutaneous sensory perception transmitted via neuropeptide-containing unmyelinated nerve fibers in the papillary dermis and epidermis. Substance P and its receptor, neurokinin receptor 1 (NK1), have been implicated by a number of preclinical and clinical studies to be important in the pathogenesis of pruritus.