Melatonin receptors in GtoPdb v.2023.1

Melatonin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Melatonin Receptors [40]) are activated by the endogenous ligands melatonin and clinically used drugs like ramelteon, agomelatine and tasimelteon

Melatonin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Melatonin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Melatonin Receptors [36]) are activated by the endogenous ligands melatonin and clinically used drugs like ramelteon, agomelatine and tasimelteon

Melatonin receptors in GtoPdb v.2021.3

Melatonin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Melatonin Receptors [40]) are activated by the endogenous ligands melatonin and clinically used drugs like ramelteon, agomelatine and tasimelteon

Allosteric site on muscarinic acetylcholine receptors: a single amino acid in transmembrane region 7 is critical to the subtype selectivities of caracurine V derivatives and alkane-bisammonium ligands.

ABSTRACT Diverse muscarinic allosteric ligands exhibit greatest affinity toward the M 2 receptor subtype and lowest affinity toward M 5 . In this study, we evaluated the potencies with which two groups of highly M 2 /M 5 selective allosteric agents modulate the dissociation of [ 3 H]N-methylscopolamine from M 2 /M 5 chimeric and point-mutated receptors. These allosteric ligands included two alkane-bisammonium compounds and a series of caracurine V derivatives, which are structurally closely related to (but stereochemically different from) the prototype allosteric ligand alcuronium. Like alcuronium, the caracurine V and alkanebisammonium compounds displayed significantly increased affinities compared with M 5 toward the chimera that included the M 2 second outer loop (o2) plus surrounding regions. Unlike alcuronium, the compounds had enhanced affinities for a chimera with M 2 sequence in transmembrane region (TM) 7; sitedirected mutagenesis in wild-type and chimeric receptors indicated that the threonine residue at M 2 423 was entirely responsible for the sensitivity toward TM7. Subsequent studies demonstrated that this TM7 epitope is likewise present in the M 4 receptor, as M 4 436 serine. The M 2 423 threonine residue is near the M 2 419 asparagine identified previously to influence gallamine binding. These studies demonstrate that a stereochemical difference can be sufficient to translate into divergent epitope sensitivities. Nonetheless, these allosteric ligands seem to derive affinity from two main regions of the receptor: o2 plus flanking regions and o3/TM7. These two epitopes are sufficient to explain the M 2 /M 5 selectivity of the presently investigated compounds; this is the first time that the subtype selectivity of muscarinic allosteric agents has been completely accounted for by distinct receptor epitopes. The five subtypes of muscarinic acetylcholine receptors are members of the superfamily of G protein-coupled receptors. The binding site for acetylcholine and conventional agonists and antagonists on muscarinic receptors seems to be located within a pocket formed by the seven ␣-helical transmembrane domains characteristic of all G protein-coupled receptors Another feature of muscarinic receptors is the presence of a second, allosteric, binding sit

Update on Melatonin Receptors. IUPHAR Review.: Melatonin Receptors

International audienceMelatonin receptors are seven transmembrane-spanning proteins belonging to the G protein-coupled receptor super-family. In mammals, two melatonin receptor subtypes exit MT1 and MT2 encoded by the MTNR1A and MTNR1B genes, respectively. The current review provides an update on melatonin receptors by the corresponding sub-committee of the International Union of Basic and Clinical Pharmacology. We will highlight recent developments of melatonin receptor ligands, including radioligands and give an update on the latest phenotyping results of melatonin receptor knockout mice. The current status and perspectives of the structure of melatonin receptor structures will be summarized. The physiological importance of melatonin receptor dimers and biologically important and type 2 diabetes-associated genetic variants of melatonin receptors will be discussed. The role of melatonin receptors in physiology and disease will be further exemplified by its functions in the immune system and the central nervous system. Finally, antioxidant and free radical scavenger properties of melatonin and its relation to melatonin receptors will be critically addressed