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Histamine H3-Receptor Antagonists as Cognitive Enhancers in Alzheimer's Disease

Ziel

The major objective of the program is to design, to develop pharmaceutically, and to assess the clinical utility of antagonists of the histamine H3-receptor (H3R) as cognitive enhancers in elderly subjects, particularly patients with Alzheimer disease.

Animal behavioural and human neuropathology data suggest that H3R antagonists, a novel class of drugs never submitted to clinical trials so far, hold promise in the field of Alzheimer's disease. They enhance histaminergic neurotransmission in the CNS, improve wakefulness and learning in animals, and histaminergic neurones seem largely spared in Alzheimer brain. Hence a novel therapeutic strategy based upon cognitive enhancement via facilitation of histamine release from relatively spared neurones.
In the present program the scientific basis for the alleged therapeutic application will be set up by i) cloning the human H3R and using it to assess the activity of already available and future, rationally-designed H3R antagonists, ii) assessing the status of the histamine receptor subtypes in Alzheimer brain by post-mortem neuropathology and PET Scan studies, two approaches for which novel probes will be developed, iii) assessing the cognitive-enhancing activity of selected H3R antagonists drugs on animal models of wakefulness, attention and learning.
The pharmaceutical development, undertaken by a novel pharmaceutical research SME, will comprise in vitro and in vivo toxicity studies, pharmacokinetics and clinical studies up to Phase II in order to validate the alleged indication.
The present project has high chances of success in spite of its novelty and short time schedule. Indeed, it involves a number of partners who i) were at the origin of the discovery of the histamine H2 and H3 receptors and design of their first ligands and radioligands, ii) are accustomed to work together on similar projects and to design and develop rapidly novel classes of drugs.

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Finanzierungsplan

CSC - Cost-sharing contracts

Koordinator

Institut National de la Santé et de la Recherche Médicale
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2 TER,CENTRE PAUL BROCA INSERM, 2TER RUE D'A
75014 PARIS
Frankreich

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Letzte Aktualisierung: 7 Mai 1996

Mein Booklet

Permalink: https://cordis.europa.eu/project/id/BMH4960204/de

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