Home LiteratureArticle Details
PMID: 3681290 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors?

Journal of neural transmission ·Vol. 70 ·No. 3-4 ·1987-00-00 ·Pages 357-68

Nilsson L, Adem A, Hardy J, Winblad B, Nordberg A

Abstract

In the presence of 9-amino-1,2,3,4-tetrahydroacridine (THA) 10(-4) M or physostigmine 10(-4) M, the in vitro 3H-Acetylcholine (3H-ACh) release from control cortical slices was significantly reduced. In contrast, THA 10(-4) M and physostigmine 10(-4) M significantly increased the release of 3H-ACh in AD/SDAT brain tissue. This facilitating effect on 3H-ACh release was partially blocked (50%) in the presence of the nicotinic antagonist d-tubocurarine 10(-6) M indicating a possible interaction via nicotinic receptors. The muscarinic antagonist atropine 10(-5) M significantly increased the 3H-ACh release both in control and AD/SDAT brains, thus indicating preservation of muscarinic autoreceptors in the AD/SDAT cortical tissue. In receptor competition studies with 3H-nicotine, 3H-ACh and 3H-quinuclidinyl benzilate (3H-QNB) as receptor ligands, THA interfered with both nicotinic and muscarinic receptor ligand binding, while physostigmine had much less effect.

MeSH Terms
Acetylcholine/metabolism Aged Alzheimer Disease/metabolism Aminoacridines/pharmacology Dementia/metabolism Female Frontal Lobe/drug effects,metabolism Humans In Vitro Techniques Male Physostigmine/pharmacology Receptors, Nicotinic/drug effects,metabolism Tacrine/pharmacology
Chemicals
Aminoacridines Receptors, Nicotinic Tacrine Physostigmine Acetylcholine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Nilsson L
Department of Pharmacology, University of Uppsala, Sweden.
Adem A
Hardy J
Winblad B
Nordberg A
References (22)
22 references, click to expand
  1. The effect of nicotine and cytisine on 3H-acetylcholine release from cortical slices of guinea-pig brain.
    Naunyn Schmiedebergs Arch Pharmacol. 1985 Nov;331(2-3):293-6 PMID: 4088325
  2. The cholinergic hypothesis--ten years on.
    Br Med Bull. 1986 Jan;42(1):63-9 PMID: 3513895
  3. Transmitter deficits in Alzheimer's disease.
    Neurochem Int. 1985;7(4):545-63 PMID: 20492959
  4. Anatoxin-a a potent ligand for nicotinic cholinergic receptors in rat brain.
    Eur J Pharmacol. 1987 Mar 31;135(3):457-8 PMID: 3582504
  5. Reduced number of [3H]nicotine and [3H]acetylcholine binding sites in the frontal cortex of Alzheimer brains.
    Neurosci Lett. 1986 Dec 3;72(1):115-9 PMID: 3808458
  6. Loss of M2 muscarine receptors in the cerebral cortex in Alzheimer's disease and experimental cholinergic denervation.
    Science. 1985 May 31;228(4703):1115-7 PMID: 3992249
  7. Cholinergic approaches to the treatment of Alzheimer's disease.
    Br Med Bull. 1986 Jan;42(1):97-100 PMID: 3006861
  8. Cortical muscarinic receptor subtypes and Alzheimer's disease.
    Lancet. 1982 Dec 4;2(8310):1277 PMID: 6128572
  9. Muscarinic receptor subtypes in hippocampus in Alzheimer's disease and mixed dementia type.
    Neurosci Lett. 1986 Sep 25;70(1):160-4 PMID: 3774212
  10. Presynaptic nicotine receptors mediating a positive feed-back on transmitter release from the rat phrenic nerve.
    Naunyn Schmiedebergs Arch Pharmacol. 1986 Dec;334(4):365-72 PMID: 2881216
  11. Metabolically active synaptosomes can be prepared from frozen rat and human brain.
    J Neurochem. 1983 Mar;40(3):608-14 PMID: 6827264
  12. The effect of cholinergic drugs on [3H]acetylcholine release from slices of rat hippocampus, striatum and cortex.
    Brain Res. 1977 Mar 11;123(2):311-22 PMID: 843927
  13. Depression of acetylcholine release from cerebral cortical slices by cholinesterase inhibition and by oxotremorine.
    Nat New Biol. 1973 Jan 24;241(108):121-2 PMID: 4512454
  14. Glucose metabolism and acetylcholine synthesis in relation to neuronal activity in Alzheimer's disease.
    Lancet. 1980 Feb 16;1(8164):333-6 PMID: 6101790
  15. Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type.
    N Engl J Med. 1986 Nov 13;315(20):1241-5 PMID: 2430180
  16. Alzheimer's disease and senile dementia: biochemical characteristics and aspects of treatment.
    Psychopharmacology (Berl). 1985;86(3):245-52 PMID: 2863836
  17. Autoregulation of acetylcholine release in isolated hippocampal nerve endings.
    Eur J Pharmacol. 1981 Jul 17;73(1):75-9 PMID: 7318890
  18. Physostigmine restores 3H-acetylcholine efflux from Alzheimer brain slices to normal level.
    J Neural Transm. 1986;67(3-4):275-85 PMID: 3806081
  19. Tubocurarine and pancuronium inhibit evoked release of acetylcholine from the mouse hemidiaphragm preparation.
    Br J Anaesth. 1987 Feb;59(2):226-31 PMID: 2881567
  20. Pre- and postsynaptic muscarinic receptors in surgical samples from human cerebral cortex.
    Brain Res. 1982 Feb 25;234(2):287-97 PMID: 6277431
  21. Different approaches to study acetylcholine release: endogenous ACh versus tritium efflux.
    Naunyn Schmiedebergs Arch Pharmacol. 1984 Dec;328(2):119-26 PMID: 6527702
  22. Nicotinic acetylcholine binding sites in Alzheimer's disease.
    Brain Res. 1986 Apr 16;371(1):146-51 PMID: 3708340
Article Info
Journal
Journal of neural transmission
Abbr.
J Neural Transm
DOI
10.1007/BF01253610
Published
1987-00-00
Pages
357-68
Language
English
Region
Austria
NLM ID
0337042
Subset
IM
External Links
PubMed source DOI: 10.1007/BF01253610
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2