Secretagogue

MK-677, an orally active spiroindoline-based growth hormone secretagogue (GHS) agonist, discovered by Merck and currently in Phase II clinical studies, was synthesized with a Fischer indolization as a key step. The synthesis of this agonist involved a Fischer indole/reduction process and was achieved in 48% overall yield from the relatively cheap starting material, isonipecotic acid 72. ... 

Carpino et al. recently disclosed the synthesis of the fused pyrazolinone-piperidine dipeptide 56 with potent growth hormone secretagogue activity. The synthesis of the intermediate pyrazolone was accomplished by reacting the ketoester 54 with methyl hydrazine in refluxing ethanol. ... 

Oral hypoglycaemic agents Oral blood glucoselowering drugs Insulin secretagogues Antihypergly-caemics... 

One intensively investigated feature of the inflammatory process in COPD is the release of proteases from neutrophils and monocytic cells that destroy elastin and other components of the interstitial matrix (Table 1). The best studied protease is neutrophil elastase. Independent of its elastolytic activity, neutrophil elastase is a potent secretagogue. More recently matrix metalloproteases (MMP) have received increasing attention, in particular MMP 12 (macrophages elastase). To which extent and how exactly these proteases become activated is not clear at present. 

SLTR1/Kir6.2 Glibenclamide and glipizide that block pancreatic KAXP channels have been used for the treatment of type II diabetes. New class of insulin secretagogues includes repaglinide and nateglinide, which improve insulin secretion, action and reduce carbohydrate absorption. 

Insulin Desensitization Insulin Receptor Insulin Resistance Insulin Secretagogues Insulin-like Growth Factor Integrase Integrin, a 4(31 Integrin, a 4(3 7 Integrin, a IIb(3 3... 

Capsazepine attenuates interstitial oedema and neutrophil infiltration in the rat pancreas following infusion of the secretagogue cerulein [150]. 

While producing the same effect as sulfonylureas, nonsulfonylurea secretagogues, also referred to as meglitinides, have a much shorter onset and duration of action. Nonsulfonylurea secretagogues also produce a pharmacologic effect by interacting with ATP-sensitive potassium channels on the (1-cells however, this binding is to a receptor adjacent to those to which sulfonylureas bind. 

Insulin secretagogue A substance or medication that stimulates insulin secretion from the pancreas. 

F21. Fukuda, Y., Hirata, Y., Yoshimi, H., Kojima, T., Kobayashi, Y Yanagisawa, M and Masaki, T., Endothelin is a potent secretagogue for atrial natriuretic peptide in cultured rat atrial myocytes. Biochem. Biophys. Res. Commun. 155,167-172 (1988). 

KW Gasser, J DiDomineco, UH Hopfer. (1988). Secretagogues activate chloride transport pathways in pancreatic zymogen granules. Am J Physiol 254 G93-G99. 

Copinschi, G., Leproult, R., Van, O. A. et al. (1997). Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Neuroendocrinology 66, 278-86. 

Guan, X. M., Yu, H., Palyha, O. C. et al. (1997). Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res. Mol. Brain Res. 48, 23-9. 

Lawrence, C. B., Snape, A. C., Baudoin, F. M. 8r Luckman, S. M. (2002). Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology 143, 155-62. 

Mitchell, V., Bouret, S., Beauvillain, J. C. et al. (2001). Comparative distribution of mRNA encoding the growth hormone secretagogue-receptor (GHS-R) in Microcebus murinus (Primate, lemurian) and rat forebrain and pituitary. J. Comp. Neurol. 429, 469-89. 

Glimepiride (Y) Amaryl Short-acting insulin secretagogues 1,2,4 1-2 0.5-1 2 8 24 hours Metabolized in liver to inactive metabolites... 

Near-normal-weight patients may be treated with insulin secretagogues. 

Failure of initial therapy should result in addition of another class of drug. Substitution of a drug from another class should be reserved for drug intolerance. Metformin and an insulin secretagogue are often first- and second-line therapy. 

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