nAChR agonist CMPI hydrochloride is a potent and selective positive allosteric modulator (PAM) of nAChR containing a α4:α4 subunit interface. nAChR agonist CMPI hydrochloride enhances the response of (α4) 3 (β2) 2 nAChR to ACh (10 μM) with an EC 50 of 0.26 μM. nAChR agonist CMPI hydrochloride has potential for the research of nicotinedependence and many neuropsychiatric conditions associated with decreased brain cholinergic activity.