Multiple actions of THA on cholinergic neurotransmission in Alzheimer brains.

A. Nordberg, L. Nilsson-Håkansson, A. Adem, Z. Lai, B. Winblad

Research output: Contribution to journalReview articlepeer-review

27 Citations (Scopus)

Abstract

1,2,3,4-tetrahydro-9-aminoacridine (THA) is a cholinesterase inhibitor presently under investigation in clinical trials for treatment of Alzheimer's disease, senile dementia of Alzheimer type (AD/SDAT). To further analyse the underlying mechanisms for its effect in human brain, an in vitro model which allows measurement of acetylcholine (ACh) release from human postmortem brain slices has been used. In control cortical tissue THA induces a decreased release of ACh probably due to negative feedback mechanisms mediated via presynaptic muscarinic autoreceptors. In AD/SDAT cortex THA enhances the release of ACh to control level. This effect is prevented by nicotinic or muscarinic receptor antagonists, which suggest receptor mechanisms involving both nicotinic and muscarinic receptors. Subchronic treatment of rats with THA (10 mg/kg sc twice daily) or physostigmine (0.9 mg/kg sc five times daily) causes a significant increase in the number of high affinity nicotinic receptors in the cortex of THA treated rats whereas no change is found in the physostigmine treated rats. The number of muscarinic receptors are decreased following both THA and physostigmine treatment.

Original languageEnglish
Pages (from-to)1169-1178
Number of pages10
JournalProgress in clinical and biological research
Volume317
Publication statusPublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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