Investigation into the in vivo effects of five novel tacrine/ferulic acid and beta-carboline derivatives on scopolamine-induced cognitive impairment in rats using radial maze paradigm.
Two tacrine-ferulic acid hybrids (1 A, 1 B) and three beta-carboline derivatives (BCs; 2A, 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. On the contrary, 1B even worsen the scopolamine induced cognition impairment. The beta-carboline derivatives 2A, 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 and 1B might act as positive allosteric modulators of scopolamine action at the muscarinic 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.
Fleck
Christian
C
Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, Germany. Christian.Fleck@mti.uni-jena.de
Appenroth
Dorothea
D
Fang
Lei
L
Schott
Yvonne
Y
Lehmann
Jochen
J
Decker
Michael
M
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000523:psychology; D003373:Coumaric Acids / Q000494:pharmacology*; D005260:Female; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology*; D013619:Tacrine / Q000494:pharmacology*
D002243:Carbolines; D003373:Coumaric Acids; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D013619:Tacrine; C004999:ferulic acid; D012601:Scopolamine