Effect of galantamine on acetylcholinesterase and butyrylcholinesterase activities in the presence of L-carnitine in rat selected brain and peripheral tissues.
OBJECTIVE
The alkaloid galantamine (GAL), which exhibits a combined anticholinesterase and direct parasympathomimetic mechanism of action, is employed in conjunction with therapeutic interventions in the stimulation of central cholinergic transfer in cognitive diseases. We attempted to achieve pharmacologically-induced enhancement of the parasympathomimetic activity of GAL in the key areas of rat brain, using an interactive combination of the alkaloid with the transmembrane enhancer L-carnitine (CAR).


METHODS
We investigated activities of acetylcholinesterase (AChE) in brain areas (frontal cortex, basal ganglia, septum and hippocampus) and the hypophysis, and that of butyrylcholinesterase (BuChE) in plasma and liver.


RESULTS
Following administration of the highest of the GAL doses used (2.5; 5; 10 mg/kg i.m.), AChE activity decreased mainly in the frontal cortex, hippocampus and hypophysis. In the interaction of GAL and CAR, AChE inhibition was stronger but without any statistical significance. The peripheral inhibition of BuChE was found to be dose-dependent. Premedication by CAR led to a slight change in the values of the activities monitored.


CONCLUSIONS
CAR in terms of positive modulation of GAL targeting to the central nervous system had no statistically significant effect.
Svoboda
Zbynek
Z
Institute of Experimental Biopharmaceutics, Joint Research Centre of Czech Academy of Sciences and PRO.MED.CS Praha a.s., Hradec Králové, Czech Republic. svoboda@uebf.cas.cz
Kvetina
Jaroslav
J
Kunesová
Gabriela
G
Herink
Josef
J
Bajgar
Jirí
J
Bartosová
Lucie
L
Zivný
Pavel
P
Palicka
Vladimír
V
D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D002091:Butyrylcholinesterase / Q000097:blood / Q000378:metabolism*; D002331:Carnitine / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005702:Galantamine / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar
D002800:Cholinesterase Inhibitors; D005702:Galantamine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002331:Carnitine