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Arzneimittelforschung 2008; 58(11): 543-550
DOI: 10.1055/s-0031-1296555
CNS-active Drugs · Hypnotics · Psychotropics · Sedatives
Editio Cantor Verlag Aulendorf (Germany)

A New Way of Data Interpretation for Cognition Tests in Rats Used to Characterise Six Choline Esterase Inhibitors with Heterocyclic Nitrogen Bridgehead Structure

Application in Alzheimer therapy
Christian Fleck
1   Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, Germany
,
Dorothea Appenroth
1   Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, Germany
,
Michael Decker
2   Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University, Jena, Germany
,
Jochen Lehmann
2   Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University, Jena, Germany
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Publikationsverlauf

Publikationsdatum:
19. Dezember 2011 (online)

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Abstract

Six new tri- and tetracyclic nitrogen bridgehead compounds known to be moderate to potent inhibitors of acetylcholinesterase (AChE) and butyrylcholin-esterase (BChE) in vitro were tested in vivo as experimental therapeutics for treatment of Alzheimer’s disease. Cognitive impairment in rats was reversibly induced by scopolamine (CAS 51-34-3). The effect of the new substances was evaluated in an eight-arm radial maze and run times (1), errors (2), correct choices (3), correct choices per second (4), speed (5), and running distance (6) were recorded. For optimisation of data analysis a new strategy was used: A score was created on the basis of the 6 parameters described with score 1 for controls and score 4 for scopolamine rats. Scores above 4 indicate an impairment of cognition function compared to scopolamine. After equimo-lar dosage compared to the reference drug rivastigmine (CAS 123441-03-2), two of the new substances slightly improved cognition in rats, but only to a significantly lower degree compared to the irreversible inhibitor rivastigmine. Surprisingly, the other four compounds did not improve or even worsened the scopolamine effect on working memory.

Key words

Acetylcholine - Acetylcholinesterase - Butyrylcholinesterase - Choline esterase inhibitors, data analysis, effect on memory - heterocyclic nitrogen bridgehead structure, radial maze, rat - Cognitive impairment, rat, scopolamine induced
 

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