Literature DB >> 16770728

The effect of mifepristone (RU 486) on plasma cortisol in Alzheimer's disease.

Nunzio Pomara1, Raymundo T Hernando, Corazon B de la Pena, John J Sidtis, Thomas B Cooper, Steven Ferris.   

Abstract

The glucocorticoid receptor (GR) antagonist mifepristone (RU-486) has been reported to increase early morning plasma ACTH/cortisol in diverse non-demented populations. This pilot study examined the cortisol response to RU 486 in patients with Alzheimer's disease (AD), a condition associated with abnormalities in various aspects of the hypothalamic-pituitary-adrenal (HPA) axis. Nine AD subjects were randomized in a placebo-controlled parallel study: 4 in the placebo group and 5 in the RU 486 group. Subjects received oral doses of RU 486 (200 mg) or placebo daily for 6-weeks. Morning plasma cortisol was determined at baseline, at 12 h following the first study drug dose, and weekly thereafter. RU 486 resulted in a significant increase in cortisol levels [F(1,6)=65.32; P<0.001]. The magnitude of this increase grew over the course of the study [F(1,6)=63.17; P<0.001], was not related to cortisol suppression after dexamethasone and appeared greater than that reported in the literature in younger populations in response to the same drug regimen. However, further studies with age-matched controls should be done to determine possible AD related changes in this response.

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Year:  2006        PMID: 16770728     DOI: 10.1007/s11064-006-9055-5

Source DB:  PubMed          Journal:  Neurochem Res        ISSN: 0364-3190            Impact factor:   3.996


  21 in total

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Authors:  M J de Leon; T McRae; H Rusinek; A Convit; S De Santi; C Tarshish; J Golomb; N Volkow; K Daisley; N Orentreich; B McEwen
Journal:  J Clin Endocrinol Metab       Date:  1997-10       Impact factor: 5.958

2.  The endocrine effects of long-term treatment with mifepristone (RU 486).

Authors:  S W Lamberts; J W Koper; F H de Jong
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Review 3.  RU486 (mifepristone): mechanisms of action and clinical uses.

Authors:  F Cadepond; A Ulmann; E E Baulieu
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4.  Glucocorticoid receptor mRNA in Alzheimer's diseased hippocampus.

Authors:  D M Wetzel; M C Bohn; A M Kazee; R W Hamill
Journal:  Brain Res       Date:  1995-05-08       Impact factor: 3.252

5.  Differences in dexamethasone-sensitivity between lymphocytes from patients with Alzheimer's disease and patients with multi-infarct dementia.

Authors:  E W Nijhuis; F Oostervink; B Hinloopen; J Rozing; L Nagelkerken
Journal:  Brain Behav Immun       Date:  1996-06       Impact factor: 7.217

Review 6.  Brain corticosteroid receptor balance in health and disease.

Authors:  E R De Kloet; E Vreugdenhil; M S Oitzl; M Joëls
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7.  RU 38486: potent antiglucocorticoid activity correlated with strong binding to the cytosolic glucocorticoid receptor followed by an impaired activation.

Authors:  M Moguilewsky; D Philibert
Journal:  J Steroid Biochem       Date:  1984-01       Impact factor: 4.292

8.  RU 486: a steroid with antiglucocorticosteroid activity that only disinhibits the human pituitary-adrenal system at a specific time of day.

Authors:  R C Gaillard; A Riondel; A F Muller; W Herrmann; E E Baulieu
Journal:  Proc Natl Acad Sci U S A       Date:  1984-06       Impact factor: 11.205

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Authors:  K R Krishnan; D Reed; W H Wilson; W B Saunders; J C Ritchie; C B Nemeroff; B J Carroll
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10.  Plasma concentrations and receptor binding of RU 486 and its metabolites in humans.

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Review 5.  Central Role of Glucocorticoid Receptors in Alzheimer's Disease and Depression.

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  5 in total

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