Serlopitant

Serlopitant is a drug that was under development for the treatment of conditions such as pruritus (itching), psoriasis, and cough. It acts as a neurokinin 1 receptor antagonist, blocking the action of substance P, a neurotransmitter thought to mediate pain and itching.

History

Serlopitant was developed by Merck & Co. and licensed to Menlo Therapeutics in 2012. In 2020, it failed to meet the primary endpoints in two Phase 3 clinical trials for pruritus associated with prurigo nodularis.

Mechanism of action

Serlopitant is a small-molecule, highly selective antagonist of the neurokinin 1 (NK1) receptor. The NK1 receptor is a G-protein coupled receptor located in key areas of the central and peripheral nervous system. Substance P, the endogenous ligand for the NK1 receptor, is involved in many physiological processes, including the transmission of pain, regulation of blood pressure, and inflammatory responses. By blocking the action of substance P, serlopitant may reduce itching, inflammation, and pain.

Clinical trials

Serlopitant has been evaluated in several clinical trials for various indications. In 2020, two Phase 3 trials for pruritus associated with prurigo nodularis failed to meet their primary endpoints. However, earlier Phase 2 studies showed promising results in reducing pruritus in patients with atopic dermatitis, psoriasis, and chronic pruritus of unknown origin.

Side effects

The most common side effects reported in clinical trials were fatigue, diarrhea, and nausea. These were generally mild and transient.

Future development

Despite the failure of the Phase 3 trials, Menlo Therapeutics has stated that they will continue to evaluate the potential of serlopitant in other indications.

See also

• Neurokinin 1 receptor
• Substance P
• Pruritus
• Psoriasis
• Cough

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