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

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

• References

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