Neurokinin 1 receptor (NK1R) (NK1R)

The Neurokinin 1 receptor (NK1R), also known as the Substance P receptor, is a member of the rhodopsin-like G protein-coupled receptor (GPCR) family and is the primary mediator for the effects of the neuropeptide Substance P [1, 4]. It is widely distributed throughout the central and peripheral nervous systems, as well as on immune cells, where it regulates critical processes such as pain transmission, neurogenic inflammation, and the emetic reflex [3, 6]. Upon binding of Substance P, the receptor activates intracellular signaling pathways, primarily through Gq/11 proteins, leading to increased calcium levels and cellular activation [15, 16]. In clinical medicine, NK1R is a well-established therapeutic target for the prevention of chemotherapy-induced and postoperative nausea and vomiting, with several approved antagonists like aprepitant and rolapitant [3, 9]. Beyond emesis, the receptor is increasingly recognized for its role in cancer progression, where its overexpression promotes tumor cell proliferation, angiogenesis, and metastasis [4, 12]. Research also highlights its involvement in psychiatric conditions such as depression and anxiety, making it a versatile target for drug development across multiple therapeutic areas [6, 14].

Other names

Tachykinin receptor 1Substance P receptorTACR1SPRNK-1R

Competitive antagonism of the Neurokinin 1 receptor, preventing the binding of the endogenous neuropeptide Substance P and subsequent downstream signaling [3, 9].