Amylin receptor 1 (AMY1 receptor (AMY1R))

Amylin receptor 1 is a heterodimeric G protein-coupled receptor composed of the calcitonin receptor (CTR) and a single-pass membrane accessory protein called RAMP1. This configuration confers high affinity for the peptide hormone amylin, which is co-secreted with insulin from pancreatic β-cells. The AMY1R can also be activated by related peptides including calcitonin gene-related peptide (CGRP), α-CGRP, β-CGRP, adrenomedullins, and calcitonins from various species; however, its highest potency is observed for human amylin and CGRP. AMY1R plays a central role in metabolic regulation—particularly appetite suppression and glucose homeostasis—and has emerged as an important therapeutic target for obesity and type 2 diabetes. The only currently approved drug targeting this pathway is pramlintide. In addition to its metabolic functions, recent research implicates AMY receptors—including AMY1R—in migraine pathophysiology due to their responsiveness to CGRP; some anti-migraine drugs designed as CGRP antagonists may also act on this target. Structurally distinct from other GPCRs due to its requirement for RAMP dimerization partners, activation of AMY receptors triggers intracellular signaling via G proteins that regulate cAMP production among other pathways. There are safety concerns regarding potential cross-reactivity between drugs targeting different members of this family—such as unintended blockade or activation during anti-migraine therapy—as well as possible roles in neurodegeneration through chronic exposure to amyloidogenic peptides. Overall, Amylin receptor 1 represents a validated therapeutic target at the intersection of metabolism and neurology but presents challenges related to selectivity within its molecular family.[3][7][8]

Other names

CTR/RAMP1Calcitonin receptor/receptor activity-modifying protein 1 complexAMY1R

Agonists mimic amylin to activate the receptor, leading to reduced food intake and improved glycemic control. Antagonists block the effects of endogenous ligands such as amylin or CGRP, potentially modulating pain pathways or neurotoxicity.