Effects of simultaneous administration of desferrioxamine and tacrine in rats.
Tacrine (1,2,3,4-tetrahydro-9-aminoacridine), a reversible cholinesterase inhibitor, was effective in the treatment of Alzheimer's disease (AD). In turn, desferrioxamine (DFO), a chelating agent with ability to chelate iron and aluminum (Al), produced a 50% decrease in the rate of cognitive decline in patients with AD. Since combined therapy with tacrine and DFO might be more effective than individual administration of these drugs for the treatment of AD patients, this study evaluated the toxic effects of concomitant administration of tacrine and DFO to rats. Three groups of 8 rats each received the following treatments for 8 w: 80 mg DFO/kg/d i.m., 7.5 mg tacrine/kg/d po, or 80 mg DFO/kg/d i.m. +7.5 mg tacrine/kg/d po. A control group received distilled water by gavage daily and a 0.9% saline injection i.m. The administration of DFO + tacrine for 8 w did not increase most of the side effects caused by the individual DFO or tacrine administrations. These results open the possibility of considering the effectiveness of simultaneous administration of DFO and tacrine as a palliative treatment for AD patients.
Laboratory of Toxicology and Environmental Health, School of Medicine, Rovira i Virgili University, Reus, Spain.
M
M
Belles
M
M
Gomez
J L
JL
Domingo
D J
DJ
Sanchez
E
E
Mayayo
J
J
Corbella
D000818:Animals; D001835:Body Weight; D002614:Chelating Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003676:Deferoxamine / Q000633:toxicity*; D004357:Drug Synergism; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013619:Tacrine / Q000633:toxicity*
D002614:Chelating Agents; D002800:Cholinesterase Inhibitors; D013619:Tacrine; D003676:Deferoxamine