Advertisement

Does Tacrine Increase Acetylcholine Release from the Hippocampus?

  • Takeshi Suzuki
  • Koichiro Kawashima
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)

Abstract

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.

Keywords

Muscarinic Receptor Choline Chloride Microdialysis Probe Hippocampal Pyramidal Neuron Muscarinic Autoreceptors 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Dawson, R.M., 1990, Reversibility of the inhibition of acetylcholinesterase by tacrine, Neurosci. Leu. 118: 85–87.CrossRefGoogle Scholar
  2. Dolezal, V., and Tucek, S., 1991, Positive and negative effects of tacrine (tetrahydroaminoacridine) and methoxytacrine on the metabolism of acetylcholine in brain cortical prisms incubated under “resting” conditions, J. Neurochem. 56: 1207–1215.PubMedCrossRefGoogle Scholar
  3. Fan, R.S., 1958, A quantitative immunological measure of the primary interaction between I*-BSA and antibody, J. Infect Dis. 103: 239–262.CrossRefGoogle Scholar
  4. Flynn, D.D., and Mash, D.C., 1989, Multiple in vitro interactions with and differential in vivo regulation of muscarinic receptor subtypes by tetrahydroaminoacridine, J. Pharmacol. Exp. Ther. 250: 573–581.PubMedGoogle Scholar
  5. Halliwell, J.V. and Grove, E.A. (1989) 9-Amino-1,2,3,4-tetrahydroacridine (THA) blocks agonist-induced potassium conductance in rat hippocampal neurones, Eur. J. Pharmacol. 163: 369–372.Google Scholar
  6. Hartvig, P., Wirklund, L., Aquilonius, S.M., and Lindstr6me, B.,1991, Clinical pharmacokinetics of centrally acting cholinesterase inhibitor, in: ’Cholinergic Basis for Alzheimer Therapy“ R. Becker and E. Giacobini eds., pp. 68–73, Birkhäuser, Boston, Basel, Berlin.Google Scholar
  7. Heilbronn, E., 1961, Inhibition of cholinesterase by tetrahydroaminoacridine, Acta Chem. Scand. 15: 1386 1390.Google Scholar
  8. James, M.K., and Cubeddu, L.X., 1987, Pharmacologic characterization and functional role of muscarinic autoreceptors in the rabbit striatum, J. Pharmacol. Exp. Ther. 240: 203–215.PubMedGoogle Scholar
  9. Kawashima, K., Ishikawa, H., and Mochizuki, M.,1980, Radioimmunoassay for acetylcholine in the rat brain, J. Pharmacol. Methods 3: 115–123.Google Scholar
  10. Loiacono, R.E., and Mitchelson, F.J., 1990, Effect of nicotine and tacrine on acetylcholine release from rat cerebral cortical slices, Naunyn-Schmiedeberg’s Arch. Pharmacol. 342: 31–35.PubMedGoogle Scholar
  11. Mayer, A., Limberger, N., and Starke, K., 1988, Transmitter release patterns of noradrenergic, dopaminergic and cholinergic axons in rabbit brain slices during short pulse trains, and the operation of presynaptic autoreceptors, Naunyn-Schmiedeberg’s Arch. Pharmacol. 338: 632–643.PubMedCrossRefGoogle Scholar
  12. Nilsson, L., Adem, A., Hardy, J., Windblad, B., and Nordberg, A., 1987, Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors? J. Neural Transm. 70: 357–368.PubMedCrossRefGoogle Scholar
  13. Perry, E.K., Smith, C.J., Court, J.A., Bonham, J.R., Rodway, M., and Atack, J.R., 1988, Interaction of 9amino-1,2,3,4-tetrahydroaminoacridine (THA) with human cortical nicotinic and muscarinic receptor binding in vitro, Neurosci. Lett. 91: 211–216.PubMedCrossRefGoogle Scholar
  14. Potter, L.T., Ferrendelli, C.A., Hanchett, H.E., Hollfield, M.A., and Lorenzi, M.V., 1989 ) Tetrahydroaminoacridine and other allosteric antagonists of hippocampal M1 muscarinic receptors, Mol. Pharmacol. 35: 652–660.PubMedGoogle Scholar
  15. Rogawski, M.A., 1987, Tetrahydroaminoacridine blocks voltage-dependent ion channels in hippocampal neurons, Eur. J. Pharmacol. 142: 169–172.PubMedCrossRefGoogle Scholar
  16. Stevens, D.R., and Cotman, C.W., 1987, Excitatory actions of tetrahydro-9-aminoacridine (THA) on hippocampal pyramidal neurons, Neurosci. Lett. 79: 301–305.PubMedCrossRefGoogle Scholar
  17. Summers, W.K., Majovski, L.V., Marsh, G. M., Tachiki, K., and Kling, A., 1986, Oral tetrahydroamino- acridine in long-term treatment of senile dementia, Alzheimer type, New Engl. J. Med. 37: 1241–1245.CrossRefGoogle Scholar
  18. Suzuki, T., Nonaka, H., Fujimoto, K., and Kawashima, K., 1993, Effects of physostigmine and some nitric oxide-cyclic GMP related compounds on muscarinic receptor-mediated autoinhibition of hippocampal acetylcholine release, J. Neurochem. 60: 2285–2289.PubMedCrossRefGoogle Scholar
  19. Tucek, S., and Dolezal, V.,1991, Negative effects of tacrine (tetrahydroaminoacridine) and methoxytacrine on the metabolism of acetylcholine in brain slices incubated under conditions stimulating neurotransmitter release, J. Neurochem. 56: 1216–1221.Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Takeshi Suzuki
    • 1
  • Koichiro Kawashima
    • 1
  1. 1.Department of PharmacologyKyoritsu College of PharmacyTokyo 105Japan

Personalised recommendations