EVP-6124 is a partial agonist of α7 neuronal nicotinic acetylcholine receptors (nAChRs) that was proved high-affinity in vitro and in vivo. EVP-6124 was proved to show selectivity for α7 but low-affinity of α4β2 nAChRs in some binding and functional experiments. EVP-6124 had good brain penetration and an adequate exposure time. Co-administration of EVP-6124 and the selective nAChRs antagonist could contribute to the release of DA, ACH, and Glu. This could be used to treat cognitive impairment and possibly other dimensions of psychopathology. Co-administration of donepezil at 0.1 mg/kg, p.o. and EVP-6124 at 0.03 mg/kg proved to be fully restored memory while each of these did not improve memory in this task. Pretreatment with the selective α7 nAChR antagonist, methyllycaconitine (MLA, 1.0 mg/kg), significantly blocked cortical DA and Glu efflux induced by EVP-6124 (0.1 mg/kg).