Methods of effecting memory enhancement mediated by steroid sulf

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai

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514182, A61K 3156, A61K 3157

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active

055568475

ABSTRACT:
This invention discloses a method for treating a patient for an illness selected from the group consisting of amnesia, head injuries, Alzheimer's disease, epileptic dementia, presenile dementia, post traumatic dementia, senile dementia, vascular dementia and post stroke dementia or individuals otherwise seeking memory enhancement. The method comprises providing a compound of formula (1) ##STR1## wherein (a) R.sub.1 and R.sub.2 are the same or different and are selected from the group consisting of hydrogen and a lower alkyl group of 1 to 6 carbon atoms and (b) the ring system ABCD is asteroid nucleus selected from the group consisting of estrone, dehydroepiandrosterone, estradiol, estradiolester, pregnenolone, substituted estrone, substituted dehydroepiandrosterone, substituted estradiol, substituted estradiolesters and substituted pregnenolone. The invention also discloses the enhancement of memory by the steroid sulfatase inhibitors of the invention acting synergistically with the naturally occurring neurosteroids dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate (PS).

REFERENCES:
Flood et al., "Dehydroepiandrosterone and its sulfate enhance memory retention in mice", Brain Research, vol. 447, pp. 269-278, 1988.
Flood et al., "Dehydroepiandrosterone sulfate improves memory in aging mice", Brain Research, vol. 448, pp. 178-181, 1988.
Flood et al., "Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it", Proc, Nat'l. Acad. Sci. USA, vol. 89, pp. 1567-1571, 1992.
Majewska, "Neurosteroids: Endogenous Bimodal Modulators of the GABA.sub.A Receptor. Mechanism of Action and Physiological Significance", Progress in Neurobiology, vol. 38, pp. 379-395, 1992.
Robel et al., "Neurosteroids: Biosynthesis and Function", Trends Endocrinol Metab, vol. 5, pp. 1-8, 1994.
Mellon, "SPECIAL ARTICLE-- Neurosteroids: Biochemistry, Modes of Action, and Clinical Relevance", Journal of Clinical Endocrinology and Metabolism, vol. 78, No. 5, pp. 1003-1008, 1994.

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