Cholinergic drugs for alzheimer's disease enhance in vitro dopamine release

Lifen Zhang, Fuming Zhou, John A. Dani

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Alzheimer's disease is a neurodegenerative disorder associated with a decline in cognitive abilities. Patients also frequently have noncognitive symptoms, such as anxiety, depression, apathy, and psychosis, that impair daily living. The most commonly prescribed treatments for Alzheimer's disease are acetylcholinesterase inhibitors, such as donepezil (Aricept; Eisai Inc., Teaneck, NJ) and galantamine (Reminyl; Janssen Pharmaceutica Products, Titusville, NJ). Enhanced cholinergic functions caused by these compounds are believed to underlie improvements in learning, memory, and attention. The noncognitive aspects of dementia, however, are usually linked to serotonin and dopamine rather than acetylcholine because those neurotransmitter systems most directly influence mood, emotional balance, and psychosis. Fast-scan cyclic voltammetry applied to mouse striatal brain slices was used to measure the real-time release of dopamine arising from spontaneous activity or from single electrical stimulations. At concentrations that include their prescribed dosage ranges, donepezil (1-1000 nM) and galantamine (50-1000 nM) increase action potential-dependent dopamine release. Consistent with previous literature, the data support slightly different modes of action for donepezil and galantamine. The ability of these commonly prescribed drugs to alter catecholamine release may underlie their influence over noncognitive symptoms of dementia. Furthermore, these results suggest that acting via nicotinic receptors, these drugs may serve presently untapped therapeutic roles by altering dopamine release in other disorders involving dopaminergic systems.

Original languageEnglish (US)
Pages (from-to)538-544
Number of pages7
JournalMolecular Pharmacology
Volume66
Issue number3
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

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Galantamine
Cholinergic Agents
Dopamine
Alzheimer Disease
Aptitude
Psychotic Disorders
Dementia
Corpus Striatum
Apathy
Cholinesterase Inhibitors
Nicotinic Receptors
Neurodegenerative Diseases
Pharmaceutical Preparations
Electric Stimulation
Action Potentials
Acetylcholine
Catecholamines
Neurotransmitter Agents
Serotonin
Anxiety

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Cholinergic drugs for alzheimer's disease enhance in vitro dopamine release. / Zhang, Lifen; Zhou, Fuming; Dani, John A.

In: Molecular Pharmacology, Vol. 66, No. 3, 01.09.2004, p. 538-544.

Research output: Contribution to journalArticle

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