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Psychopharmacology (Berl). 2017 Aug;234(15):2365-2374. doi: 10.1007/s00213-017-4664-z. Epub 2017 Jun 19.

Co-modulation of an allosteric modulator of nicotinic receptor-cholinesterase inhibitor (galantamine) and a 5-HT4 receptor agonist (RS-67333): effect on scopolamine-induced memory deficit in the mouse.

Author information

1
Normandie University, UNICAEN, INSERM, COMETE, 14000, Caen, France. thomas.freret@unicaen.fr.
2
Normandie University, UNICAEN, INSERM, COMETE, 14000, Caen, France.

Abstract

AIM:

It is widely assumed that the upcoming therapeutics for Alzheimer's disease will require to act on more than one target to be effective. We investigated here whether a combination of the nicotinic receptor allosteric modulator/cholinesterase inhibitor galantamine can act synergistically with the type 4 serotonin receptor (5-HT4R) partial agonist, RS-67333, to counterbalance deficits in short- and long-term memory. To select sub-efficacious doses of both drugs, dose-response studies were first performed on the scopolamine-induced deficits of spontaneous alternation in the Y-maze task and of acquisition and retrieval processes in a passive avoidance task.

RESULT:

For spontaneous alternation behavior, combination of 1 mg/kg galantamine and 0.5 mg/kg RS-67333 fully reversed the deficit. In the passive avoidance task, no sub-efficacious doses could be found in the retention paradigm, but a beneficial effect of the association has been demonstrated in the acquisition paradigm.

CONCLUSION:

Mnesic effects of galantamine can be thus potentiated by activation of 5-HT4R. Such a combination treatment might (1) strengthen symptomatic relief, (2) attenuate adverse effects given the lower doses of each compound required, and (3) afford a disease-modifying effect given the known action of 5-HT4R on amyloidogenesis cascade.

KEYWORDS:

Acetylcholinesterase inhibitor; Behavior; Memory; Neurodegenerative; Serotonin

PMID:
28631100
DOI:
10.1007/s00213-017-4664-z
[Indexed for MEDLINE]

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