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• W1968896739 endingPage "1618" @default.
• W1968896739 startingPage "1599" @default.
• W1968896739 abstract "The 28 amino acid polypeptide, ghrelin, is a novel neuroendocrine hormone synthesised primarily in the stomach. It stimulates growth hormone (GH) secretion, increases food intake and appetite and promotes body weight gain by decreasing fat mass metabolism, particularly in rodent models. The pharmacological properties of this peptide are mediated by the type 1a growth hormone secretagogue receptor (GHS-R1a), a G-protein-coupled receptor localised predominantly in the pituitary gland and hypothalamus. The discovery of new agents that either mimic or modulate the actions of ghrelin via the GHS-R1a has attracted considerable interest in recent years. Many peptidyl and peptidomimetic GHS-R1a agonists such as growth hormone-releasing peptides (GHRPs) and growth hormone secretagogues (GHSs) that stimulate GH secretion and increase plasma levels of insulin-like growth factor-1 (IGF-1) have been identified. First generation GHSs have undergone extensive clinical evaluation in humans, but have shown disappointing results in the treatment of diseases such as frailty, the age-related decline in body composition. Several of these compounds were found to increase adiposity in rodent models. Second generation dipeptidyl and third generation small molecule GHSs have recently been profiled in various animal models. A third generation of GHS with partial agonist activity at the GHS-R1a showed anabolic activity in rodent models, increasing fat-free (muscle) mass rather than fat mass. A few GHS-R1a receptor antagonists have been disclosed, although these compounds have exhibited poor selectivities or weak affinities for the receptor. Since endogenous ghrelin appears to play an important role in the long-term regulation of energy balance, GHS-R1a antagonists may be useful in the prevention of weight gain, following weight loss, or in the treatment of obesity, a pathological condition characterised by excess adiposity. This review describes the pharmacology of select ghrelin receptor modulators and highlights new ghrelin receptor agonists and antagonists that have appeared in the literature from 1999 – 2002." @default.
• W1968896739 created "2016-06-24" @default.
• W1968896739 creator A5035773588 @default.
• W1968896739 date "2002-11-01" @default.
• W1968896739 modified "2023-10-11" @default.
• W1968896739 title "Recent developments in ghrelin receptor (GHS-R1a) agonists and antagonists" @default.
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• W1968896739 doi "https://doi.org/10.1517/13543776.12.11.1599" @default.
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