Showing papers on "Growth hormone secretagogue published in 1995"
TL;DR: A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized and has been selected for clinical studies.
Abstract: A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized. L-163,191 releases GH from rat pituitary cells in culture with EC50 = 1.3 +/- 0.09 nM and is mechanistically indistinguishable from the GH-releasing peptide GHRP-6 and the prototypical nonpeptide GH secretagogue L-692,429 but clearly distinguishable from the natural GH secretagogue, GH-releasing hormone. L-163,191 elevates GH in dogs after oral doses as low as 0.125 mg/kg and was shown to be specific in its release of GH without significant effect on plasma levels of aldosterone, luteinizing hormone, thyroxine, and prolactin after oral administration of 1 mg/kg. Only modest increases in cortisol were observed. Based on these properties, L-163,191 has been selected for clinical studies.
330 citations
TL;DR: Results show that L-692,429 increases hormone secretion by human pituitary cells via a protein kinase C and Ca2+ dependent mechanism.
56 citations
TL;DR: The GH-secretagogue-induced c-fos mRNA in the brain of these mutants are unlikely to be mediated by an indirect action of GH or a interaction of the synthetic GH- secretagogue with the GHRH receptor.
Abstract: We have studied by in situ hybridization histochemistry the mRNA expression of the c-fos immediate early gene in the brains of wild type and dwarf(dw/dw) and little(lit/lit) mutant mice after systemic injections of the synthetic GH secretagogues GHRP-6 and L-163,191. Both GH secretagogues induced a marked c-fos mRNA expression in the arcuate-ventromedial hypothalamus (ARC-VMH) of both control and mutant mice indicating a possible action on growth hormone releasing hormone (GHRH) neurones in the ARC-VMH. Both dw/dw and lit/lit mice showed a 5-fold elevation in GHRH mRNA expression in the ARC-VMH compared with control animals under basal conditions. Since lit/lit mice have a reduced ability to secrete GH and lack a functional GHRH receptor while dw/dw mice lack both GH and presumably GHRH receptors, the GH-secretagogue-induced c-fos mRNA in the brain of these mutants are unlikely to be mediated by an indirect action of GH or a interaction of the synthetic GH-secretagogue with the GHRH receptor.
19 citations
TL;DR: In this article, a practical, convergent synthesis of L-692,429 from three key intermediates -the 3- aminobenzlactam 2, the β lactam 3 and the biphenyltetrazole 4 is described.
12 citations
TL;DR: Substitution of the 5-position with a carbonyl group or hydroxyl group and replacement of the benzolactam with the 1,4-benzodiazapin-2-one ring system gave analogs of greatly diminished in vitro activity.
12 citations
TL;DR: A radioimmunoassay method for hexarelin, a peptidic growth hormone secretagogue, has been developed and applied to pharmacokinetic studies in dogs following an IV dose of 1 microgram/kg, and three SC doses of 1, 10, and 100 micrograms/kg.
5 citations
TL;DR: It is suggested that the specific activation of delta-opioid receptors in man may exert an inhibitory influence on GH secretion principally by modulating endogenous hypothalamic somatostatin (SRIH) release.
3 citations
TL;DR: In this paper, a highly efficient synthesis of the potent Human Growth Hormone Secretagogue L-692, 585 1 via a Micheal addition with a 3,3-dimethyl acrylic acid derivative 7 and (R)-1-amino-2-propanol 2 is presented.
2 citations