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Arzneimittelforschung 2010; 60(6): 299-306
DOI: 10.1055/s-0031-1296291
CNS-active Drugs · Hypnotics · Psychotropics · Sedatives
Editio Cantor Verlag Aulendorf (Germany)

Investigation into the in vivo effects of five novel tacrine/ferulic acid and β-carboline derivatives on scopolamine-induced cognitive impairment in rats using radial maze paradigm

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
,
Lei Fang
2   Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University, Jena, Germany
3   School of Chemistry and Chemical Engineering, South-East University, Nanjing, P. R. China
,
Yvonne Schott
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
,
Michael Decker
2   Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University, Jena, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
02 December 2011 (online)

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Abstract

Two tacrine-ferulic acid hybrids (1 A, 1 B) and three β-carboline derivatives (BCs;2 A, 2B, 2C) were tested in vivo on 3-month-old female rats as multi-potent anti-Alzheimer drug candidates. In vitro, the two tacrine-ferulic acid hybrids show higher acetylcholinesterase (AChE) inhibitory activity and comparable butyrylcholinesterase (BChE) inhibitory activity compared to tacrine (CAS 1684-40-8). However, in vivo both substances have no beneficial effect on scopolamine (CAS 51-34-3) induced cognition impairment. Onthe contrary, 1B even worsen the scopolamine induced cognition impairment The β-carboline derivatives 2 A, 2B, and 2 C, the inhibitory potency of which at AChE reaching tacrine activity does not antagonize scopolamine induced impairment of cognition in rats measured in radial maze paradigm. Compounds 2A and1 B might act as positive allosteric modulators of scopolamine action at the mus-carinic acetylcholine receptors. On the basis of these results it can be concluded that both ferulic acid- (CAS 537-98-4) and BC-derivatives are not qualified as cognition improving drugs and further studies in this field should be focussed on other pharmaceutical leads to find effective anti-Alzheimer drugs.

Key words

Anti-Alzheimer drugs - Antioxidants - b-Carbolines - Cholinesterase inhibitors - Ferulic acid, hybrid molecule,rat - Tacrine, hybrid molecule, rat
 

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