A putative new melatonin binding site in sheep brain, MTx: preliminary observations and characteristics.

In mammals, MT and MT melatonin receptors are high affinity G protein-coupled receptors and are thought to be involved in the integration of the melatonin signaling throughout the brain and periphery. In the present study, we describe a new melatonin binding site, named MTx, with a peculiar pharmacological profile. This site had a low affinity for 2-[I]-melatonin in saturation assays in hypothalamus and retina (pK = 9.

Mechanistic characterization of S 38093, a novel inverse agonist at histamine H3 receptors.

Histaminergic H3 inverse agonists, by stimulating central histamine release, represent attractive drug candidates to treat cognitive disorders. The present studies aimed to describe the mechanistic profile of S 38093 a novel H3 receptors inverse agonist. S 38093 displays a moderate affinity for rat, mouse and human H3 receptors (Ki=8.

Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models.

The compound S38151 is a nanomolar antagonist that acts at the melanin-concentrating hormone receptor 1 (MCH(1)). S38151 is more stable than its purely peptide counterpart, essentially because of the blockade of its N-terminus. Therefore, its action on various models of obesity was studied.

S32212, a novel serotonin type 2C receptor inverse agonist/α2-adrenoceptor antagonist and potential antidepressant: I. A mechanistic characterization.

Although most antidepressants suppress serotonin (5-HT) and/or noradrenaline reuptake, blockade of 5-HT(2C) receptors and α(2)-adrenoceptors likewise enhances monoaminergic transmission. These sites are targeted by the urea derivative N- [4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-1,2-dihydro-3-H-benzo[e]indole-3-carboxamide (S32212). S32212 was devoid of affinity for monoamine reuptake sites, yet displayed pronounced affinity (pK(i), 8.