Characterisation of dopamine and serotonin uptake inhibitory effects of tetrahydroaminoacridine in rat brain.
The effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on uptake rates of radioactive 5-hydroxytryptamine (5-HT) and dopamine were investigated in rat diencephalon and striatal homogenates, respectively. Six and eight microM of THA were needed to inhibit 50% of dopamine and 5-HT uptake rates. Kinetic parameters, Km and Vmax, using six different concentrations of dopamine and 5-HT were estimated in the presence or absence of THA. A significant decrease in Vmax without any change in Km values was observed for both dopamine and 5-HT in the presence of THA. The results show that THA is a non-competitive uptake inhibitor of dopamine and 5-HT in the nerve terminals. The re-uptake blocking effect of THA on dopaminergic and serotonergic neurones, following THA treatment, might lead to increased levels of these monoamines in brains of Alzheimer patients and contribute in the therapeutic effects of the drug.
Jossan
S S
SS
Department of Medical Pharmacology, University of Uppsala, Sweden.
Adem
A
A
Winblad
B
B
Oreland
L
L
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004027:Diencephalon / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013619:Tacrine / Q000494:pharmacology*
D004298:Dopamine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013619:Tacrine