TY - JOUR
TI - Mapping the melatonin receptor. 7. Subtype selective ligands based on β-substituted N-acyl-5-methoxytryptamines and β-Substituted N-acyl-5-methoxy-1-methyltryptamines
AU - Tsotinis, A.
AU - Vlachou, M.
AU - Papahatjis, D.P.
AU - Calogeropoulou, T.
AU - Nikas, S.P.
AU - Garratt, P.J.
AU - Piccio, V.
AU - Vonhoff, S.
AU - Davidson, K.
AU - Teh, M.-T.
AU - Sugden, D.
JO - Journal of Medicinal Chemistry
PY - 2006
VL - 49
TODO - 12
SP - 3509-3519
PB - 
SN - 0022-2623, 1520-4804
TODO - 10.1021/jm0512544
TODO - 5 methoxytryptamine;  beta methylmelatonin;  beta,beta dimethylmelatonin;  melatonin 1 receptor;  melatonin 2 receptor;  melatonin derivative;  melatonin receptor;  n acyl 5 methoxy 1 methyltryptamine derivative;  n acyl 5 methoxytryptamine derivative;  n butanoyl 5 methoxy 1 methyl beta,beta tetramethylenetryptamine;  n butanoyl 5 methoxy 1 methyl beta,beta trimethylenetryptamine;  unclassified drug, animal cell;  article;  binding assay;  binding site;  cell strain 3T3;  controlled study;  drug potency;  drug receptor binding;  embryo;  human;  human cell;  melanophore;  molecular cloning;  mouse;  nonhuman;  protein expression;  protein localization;  Xenopus laevis, Animals;  Binding Sites;  Cell Line;  Humans;  Ligands;  Melanophores;  Melatonin;  Mice;  Molecular Conformation;  NIH 3T3 Cells;  Pigments, Biological;  Radioligand Assay;  Receptor, Melatonin, MT1;  Receptor, Melatonin, MT2;  Recombinant Proteins;  Stereoisomerism;  Structure-Activity Relationship;  Tryptamines;  Xenopus laevis
TODO - A series of β-substituted and β,β-disubstituted N-acyl 5-methoxy-1-methyltryptamines and 5-methoxytryptamines have been prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor. The affinity of analogues was determined in a radioligand binding assay using cloned human MT1 and MT2 receptor subtypes expressed in NIH 3T3 cells. Agonist and antagonist potency of all analogues was measured using the pigment aggregation response of a clonal line of Xenopus laevis melanophores, β-Methylmelatonin (17a) and β,β-dimethylmelatonin (17b), though showing a slight decrease in binding at human receptors, show an increase in potency on Xenopus, N-Butanoyl 5-methoxy-1-methyl-β,β-trimethylenetryptamine (12c) is an antagonist at human MT1 receptors but an agonist at MT2, while N-butanoyl 5-methoxy-1-methyl-β,β-tetramethylenetryptamine (13c) is an antagonist at MT1 but had no action at MT2 and is one of the first examples of an MT1 selective antagonist. © 2006 American Chemical Society.
ER -