Increased effectiveness of tacrine by deprenyl co-treatment in rats: EEG and behavioral evidence
by
Dringenberg HC, Laporte PP, Diavolitsis P
Department of Psychology,
Queen's University, Kingston,
Ontario, Canada.
Neuroreport 2000 Nov 9;11(16):3513-6
ABSTRACTThe acetylcholinesterase inhibitor tacrine and the monoamine oxidase inhibitor deprenyl are considered useful pharmacotherapies for Alzheimer's disease (AD). We assessed whether co-administration of these two compounds increases their effectiveness against two measures of cholinergic-monoaminergic hypofunction in rats, cortical EEG slowing and impaired spatial performance. EEG slowing induced by cholinergic-monoaminergic blockade was reversed by both deprenyl (10 - 50 mg/kg) and tacrine (1 - 20 mg/kg), but co-treatment with a subthreshold dose of deprenyl plus tacrine was markedly more effective. Neither tacrine (5 mg/kg) nor deprenyl (10 mg/kg) alone reduced water maze deficits due to cholinergic-monoaminergic hypofunction, but co-treatment (using these doses) improved performance. Cholinergic-monoaminergic co-treatment may constitute a useful pharmacotherapy to correct physiological and behavioral dysfunction due to neurotransmitter deficiencies in AD.Structure
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