Abstract |
Data derived from a number of preclinical studies examining the effects of combined cholinergic and noradrenergic lesions in a rat model of Alzheimer's disease are reviewed. Results from these studies indicated that a nucleus basalis of Meynert (nbM) lesion combined with a lesion of the ascending noradrenergic bundle (ANB) did not exacerbate 72-h passive avoidance retention deficits beyond the degree of impairment produced by nbM lesions alone. However, the addition of an ANB lesion did block the efficacy of two choiinomimetics ( physostigmine and oxotremorine) to reverse the lesion-induced memory impairment. Memory in combined lesioned rats was restored when cholinomimetic therapy was administered in combination with low doses of clonidine. Studies investigating a number of Hoechst-Roussel Pharmaceuticals compounds have produced memory-enhancing effects in animals prepared with combined nbM/ANB lesions without the need for clonidine supplementation. These compounds include P128, P86-7493, and P87-8184. Moreover, these compounds have also been shown to be effective in reversing passive avoidance memory deficits in animals with nbM lesions and treated with the noradrenergic toxin DSP-4. Implications for pharmacotherapeutic approaches for the treatment of Alzheimer's disease are discussed.
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Authors | A C Santucci, V Haroutunian, K L Davis |
Journal | Clinical neuropharmacology
(Clin Neuropharmacol)
Vol. 14 Suppl 1
Pg. S1-8
( 1991)
ISSN: 0362-5664 [Print] United States |
PMID | 1913705
(Publication Type: Journal Article)
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Chemical References |
- Benzylamines
- Cholinergic Agents
- Organic Chemicals
- P 86-7493
- P 87-8184
- Parasympathomimetics
- Oxotremorine
- Physostigmine
- Clonidine
- DSP 4
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Topics |
- Alzheimer Disease
(physiopathology)
- Animals
- Avoidance Learning
(drug effects)
- Benzylamines
(pharmacology)
- Cholinergic Agents
- Cholinergic Fibers
(drug effects)
- Clonidine
(pharmacology)
- Disease Models, Animal
- Male
- Memory
(drug effects)
- Organic Chemicals
- Oxotremorine
(pharmacology)
- Parasympathomimetics
(pharmacology)
- Physostigmine
(pharmacology)
- Rats
- Rats, Inbred Strains
- Substantia Innominata
(drug effects)
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