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Synergistic effect of acetylcholinesterase inhibition (donepezil) and 5-HT4 receptor activation (RS67333) on object recognition in mice
- Source :
- Behavioural Brain Research, Behavioural Brain Research, Elsevier, 2012, 230, pp.304-308, Behavioural Brain Research, Elsevier, 2012, 230 (1), pp.304-8. ⟨10.1016/j.bbr.2012.02.012⟩, HAL
- Publication Year :
- 2012
- Publisher :
- HAL CCSD, 2012.
-
Abstract
- International audience; Facing inefficiency of current treatments to cure Alzheimer disease (AD), a pharmacological approach is now emerging on the assumption that a single compound may be able to hit multiple targets, namely Multi-Target-Directed Ligands (MTDLs). Displaying numerous advantages, several MTDL for AD have been recently described but none associating an inhibition of AChE and an activation of 5-HT(4)R. The aim of this study was to validate the concept of a synergistic action of these two targets on episodic-like memory performances in mice. Among potent molecules, RS67333, a reference 5-HT(4)R agonist and donepezil (DNPZ), a reference acetylcholinesterase inhibitor, have been particularly chosen because of their close chemical structure. Administered separately, RS67333 (0.3 and 1mg/kg) and DNPZ (1mg/kg) improved recognition performances compared to saline treated animals but not with lower doses. Co-administration of subactive doses of RS67333 (0.1mg/kg) and DNPZ (0.3mg/kg) improved memory, moreover, this improvement is prevented if a 5-HT(4)R antagonist (GR125487, 10mg/kg) is also administered. Activation of 5-HT(4)R combined with inhibition of AChE with subactive doses of RS67333 and of DNPZ has synergistic effects on memory performances in mice. These molecules having close chemical structures, the synergistic effect of their combination affords new hope to chemist for the synthesis of MTDL.
- Subjects :
- Agonist
Male
Indoles
medicine.drug_class
Aché
Pharmacology
03 medical and health sciences
Behavioral Neuroscience
chemistry.chemical_compound
Mice
0302 clinical medicine
Piperidines
medicine
Animals
Donepezil
5-HT receptor
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
0303 health sciences
Analysis of Variance
Sulfonamides
Aniline Compounds
Behavior, Animal
Dose-Response Relationship, Drug
Chemistry
[SCCO.NEUR]Cognitive science/Neuroscience
Antagonist
Drug Synergism
Recognition, Psychology
Acetylcholinesterase
language.human_language
3. Good health
Serotonin Receptor Agonists
Dose–response relationship
Acetylcholinesterase inhibitor
Indans
language
Cholinesterase Inhibitors
Serotonin Antagonists
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 01664328 and 18727549
- Database :
- OpenAIRE
- Journal :
- Behavioural Brain Research, Behavioural Brain Research, Elsevier, 2012, 230, pp.304-308, Behavioural Brain Research, Elsevier, 2012, 230 (1), pp.304-8. ⟨10.1016/j.bbr.2012.02.012⟩, HAL
- Accession number :
- edsair.doi.dedup.....1c792896e3eb5f1d69878b4de4b9dc54