Does Tacrine Increase Acetylcholine Release from the Hippocampus?
Tacrine (9-amino-1,2,3,4-tetrahydroacridine) has been investigated as a therapeutic agent for memory impairment in Alzheimer’s disease (Summers et al., 1986). It is a centrally active cholinesterase inhibitor (Heilbronn, 1961; Dawson, 1990), and other effects such as blockade of some types of cation channel (Rogawski, 1987; Stevens and Cotman, 1987; Halliwell and Grove, 1989) and inhibition of nicotinic (Nilsson et al., 1987; Perry et al., 1988) and muscarinic ligand binding (Flynn and Mash, 1989; Potter et al., 1989) have been reported. Due to its anticholinesterase activity, tacrine should increase the extracellular concentration of acetylcholine (ACh), like other cholinesterase inhibitors. It has been found that an increase in the extracellular concentration of ACh, or application of muscarinic agonists, inhibits ACh release from the nerve terminal (James and Cubeddu, 1987; Mayer et al., 1988). Previous researchers have reported that tacrine inhibits depolarization-induced ACh release (Loiacono and Mitchelson, 1990; Tucek and Dolezal, 1991), although these observations would be against the clinical usefulness of tacrine. In this study, we tested the effects of tacrine on ACh release from rat hippocampal slices to clarify its pharmacological profile.
KeywordsMuscarinic Receptor Choline Chloride Microdialysis Probe Hippocampal Pyramidal Neuron Muscarinic Autoreceptors
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