Home HOME General Physiology and Biophysics 2015 General Physiology and Biophysics Vol.34, No.2, p.189–200, 2015

Journal info


Quarterly, 80 pp. per issue
Founded: 1982
ISSN  1338-4325 (online)

Published in English

Aims and Scope
Editorial Info
Abstracting and Indexing
Submission Guidelines

Select Journal







Webshop Cart

Your Cart is currently empty.

Info: Your browser does not accept cookies. To put products into your cart and purchase them you need to enable cookies.

General Physiology and Biophysics Vol.34, No.2, p.189–200, 2015

Title: Cholinergic properties of new 7-methoxytacrine-donepezil derivatives
Author: Vendula Sepsova, Jana Z. Karasova, Gunnar Tobin, Daniel Jun, Jan Korabecny, Pavla Cabelova, Katerina Janska, Jan Krusek, Kristyna Skrenkova, Kamil Kuca, Marian Valko, Ondrej Soukup

Abstract: Organophosphorus nerve agents inhibit acetylcholinesterase (AChE) which causes the breakdown of the transmitter acetylcholine (ACh) in the synaptic cleft. Overstimulation of cholinergic receptors (muscarinic and nicotinic) by excessive amounts of ACh causes several health problems and may even cause death. Reversible AChE inhibitors play an important role in prophylaxis against nerve agents. The presented study investigated whether 7-methoxytacrine (7-MEOTA) and 7-MEOTA-donepezil derivatives can act as central and peripheral reversible AChE inhibitors and simultaneously antagonize muscarinic and nicotinic receptors. The possible mechanism of action was studied on cell cultures (patch clamp technique, calcium mobilization assay) and on isolated smooth muscle tissue (contraction study). Furthermore, the kinetics of the compounds was also examined. CNS availability was predicted by determining the passive blood-brain barrier penetration estimated via a modified PAMPA assay. In conclusion, this study provides promising evidence that the new synthesized 7-MEOTA-donepezil derivatives have the desired anticholinergic effect; they can inhibit AChE, and nicotinic and muscarinic receptors in the micromolar range. Furthermore, they seem to penetrate readily into the CNS. However, their real potency and benefit must be verified by in vivo experiments.

Keywords: Acetylcholinesterase inhibitors — Nicotinic receptors — Muscarinic receptors — Bladder — Prophylaxis
Year: 2015, Volume: 34, Issue: 2 Page From: 189, Page To: 200
doi:10.4149/gpb_2014036


download file



© AEPress s.r.o
Copyright notice: For any permission to reproduce, archive or otherwise use the documents in the ELiS, please contact AEP.