Growth hormone secretagogues: mechanism of action and use in aging.
GH secretagogues present a tool for furthering our understanding of the control of GH secretion, as well as a unique therapeutic opportunity. These compounds activate the receptors of a putative endogenous ligand in the hypothalamus and pituitary. Acting as functional somatostatin antagonists, GH secretagogues potentiate the actions of GHRH on GH secretion, enhancing pulsatile GH secretion. The clinical target of the elderly population presents significant challenges to drug development. Age-related musculoskeletal impairment as a result of muscle wasting (sarcopenia) is not well recognized as a clinical syndrome. In addition, given the inherent day to day variability in function in the "frail" target population as well as the presence of a host of concomitant conditions, the appropriate patient population to be studied remains to be defined, and demonstration of clinically meaningful efficacy may be difficult. It is not clear whether it will be useful to restore to young levels the activity of the GHIGF-I axis in aging. Nevertheless, if beneficial effects on strength, similar to those demonstrated with GH79 can be shown, GH secretagogues could provide a well-tolerated clinical approach for treating or preventing sarcopenia, and perhaps, even forestall the inevitability of age-associated decline in function and independence. Such efficacy would have a great social impact.
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Merck Research Laboratories, Rahway NJ 07065, USA. vivian_fuh@merck.com
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D000368:Aged; D000375:Aging / Q000187:drug effects*; D000818:Animals; D001552:Benzazepines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D016330:Frail Elderly; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000819:agonists* / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009133:Muscular Atrophy / Q000188:drug therapy / Q000209:etiology; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000502:physiology; D013141:Spiro Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
D001552:Benzazepines; D007211:Indoles; D009842:Oligopeptides; D013141:Spiro Compounds; D013777:Tetrazoles; C086184:hexarelin; D019382:Human Growth Hormone; C081455:L 692429; C041048:growth hormone releasing hexapeptide; D013004:Somatostatin; D011388:Prolactin; C094817:ibutamoren mesylate; D006854:Hydrocortisone