9.A.14.1.3
Melatonin receptor type 1A, or MT1 (MR) of 350 aas and 7 TMSs.  Although the MT1 and 5-HT receptors have similar endogenous ligands, and agomelatine acts on both receptors, the receptors differ markedly in the structure and composition of their ligand pockets; in MT1, access to the ligand pocket is tightly sealed from solvent by extracellular loop 2, leaving only a narrow channel between transmembrane helices IV and V that connects it to the lipid bilayer (Stauch et al. 2019). The binding site is extremely compact, and ligands interact with MT1 mainly by strong aromatic stacking with Phe179 and auxiliary hydrogen bonds with Asn162 and Gln181. Free-energy simulations support a lipophilic binding route for melatonin receptors (Elisi et al. 2021). Blockage of MRs abolishes its antiarrhythmic effect and slows ventricular conduction in rat hearts (Durkina et al. 2023).