3-Furan-2-yl-N-p-tolyl-acrylamide, a positive allosteric modulator of the α7 nicotinic receptor, reverses schizophrenia-like cognitive and social deficits in rats.

Abstract	The cognitive impairments and negative symptoms experienced by schizophrenia patients still await effective treatment. Alpha7 nicotinic acetylcholine receptors (α7 nAChRs) have gain considerable attention in this regard. It has been recently proposed that positive allosteric modulators (PAMs) of α7 nAChRs may represent an alternative strategy to that based on orthosteric agonists. The aim of the present study is to evaluate the efficacy of PAM-2 (3-furan-2-yl-N-p-tolyl-acrylamide) against cognitive deficits and negative-like symptoms in a rat model of schizophrenia based on administration of ketamine, a NMDAR antagonist. The activity of PAM-2 was compared to that elicited by DMXBA, an α7 nAChR partial agonist. For this purpose, the attentional set-shifting task (ASST) and the novel object recognition task (NORT) were used. The efficacies of PAM-2 and DMXBA against ketamine-induced social withdrawal were assessed using the social interaction test (SIT). The results demonstrated that PAM-2 and DMXBA ameliorated ketamine-induced cognitive impairments on the ASST and NORT as well as produced pro-social activities in the SIT. Moreover, the co-administration of inactive doses of PAM-2 and antipsychotic drugs, clozapine or risperidone, reversed ketamine-induced deficits. The present findings provide further support for the concept that α7-PAMs could be used either alone or in combination with antipsychotics for schizophrenia therapy.
Authors	Agnieszka Potasiewicz, Małgorzata Hołuj, Tomasz Kos, Piotr Popik, Hugo R Arias, Agnieszka Nikiforuk
Journal	Neuropharmacology (Neuropharmacology) Vol. 113 Issue Pt A Pg. 188-197 (02 2017) ISSN: 1873-7064 [Electronic] England
PMID	27717880 (Publication Type: Journal Article)
Copyright	Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Chemical References	3-furan-2-yl-N-p-tolylacrylamide Acrylamides Antipsychotic Agents Benzylidene Compounds Furans Pyridines Receptors, N-Methyl-D-Aspartate alpha7 Nicotinic Acetylcholine Receptor Ketamine 3-(2,4-dimethoxybenzylidene)anabaseine
Topics	Acrylamides (administration & dosage, therapeutic use) Allosteric Regulation (drug effects) Animals Antipsychotic Agents (administration & dosage, therapeutic use) Attention (drug effects) Benzylidene Compounds (administration & dosage) Cognition (drug effects) Disease Models, Animal Furans (administration & dosage, therapeutic use) Ketamine (administration & dosage) Male Pyridines (administration & dosage) Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate (agonists) Recognition, Psychology (drug effects) Schizophrenia (chemically induced, physiopathology, prevention & control) Schizophrenic Psychology Social Behavior alpha7 Nicotinic Acetylcholine Receptor (agonists)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!