Differential effects of physostigmine and 1,2,3,4-tetrahydro-9-aminoacridine on the beta-adrenoceptor transduction system.
The effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) and physostigmine on beta-adrenoceptor-linked cyclic AMP accumulation have been analyzed in vitro in rat cortex and hippocampus. A 10-min incubation with increasing concentrations of THA reduced isoprenaline (10 microM)-stimulated cyclic AMP accumulation in a concentration-dependent manner in cortical (IC50 = 1.31 +/- 0.13 microM) and hippocampal (IC50 = 0.02 +/- 0.003 microM) structures. Conversely, physostigmine did not modify cyclic AMP synthesis in any experimental condition. The action of THA was non-competitive since it induced a non-parallel shift to the right of the concentration-response curve for isoprenaline. The differential effects of THA and physostigmine on the beta-adrenoceptor transduction system may account for the difference in their ability to restore cognitive function.
Vivas
N M
NM
Department de Farmacologia i Psiquiatria, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Badia
A
A
Màrmol
F
F
Dierssen
M
M
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013619:Tacrine / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D013619:Tacrine; D010830:Physostigmine