Mas-related G-protein coupled receptor member X1 (MRGPRX1) (MRGPRX1)

Mas-related G-protein coupled receptor member X1 (MRGPRX1) is a primate-specific Class A G protein-coupled receptor primarily expressed in the small-diameter neurons of the dorsal root ganglia and trigeminal ganglia [1, 5, 10]. It serves as a critical mediator of sensory signals, particularly non-histaminergic itch and nociception [5, 11, 16]. Unlike traditional opioid receptors, MRGPRX1 offers a therapeutic pathway for pain management that avoids typical side effects like respiratory depression or addiction, making it a highly attractive non-opioid target [1, 5, 8]. The receptor exhibits a dual role depending on its anatomical location: peripheral activation by ligands such as the antimalarial drug chloroquine or BAM8-22 triggers itch, whereas central activation at the spinal cord terminals inhibits persistent inflammatory and neuropathic pain transmission [1, 4, 8]. Current pharmacological strategies focus on utilizing agonists or positive allosteric modulators (PAMs) for analgesia, while antagonists are being investigated to treat chronic pruritus conditions like atopic dermatitis [4, 8, 11]. However, the lack of an endogenous rodent ortholog presents significant challenges for preclinical drug translation and safety assessment [1, 4, 8].

Other names

MRGPRX1SNSR1SNSR2MRGX1Mas-related gene X1 receptorSensory neuron-specific G-protein coupled receptor 1hMRGPRX1

Agonism or positive allosteric modulation of MRGPRX1 at central spinal terminals to inhibit nociceptive signaling for pain relief, or antagonism of peripheral receptors to alleviate non-histaminergic chronic itch [1, 4, 8, 11].