The α7 nicotinic acetylcholine receptor (nAChR) has been implicated in the development of various neurodegenerative disorders such as Alzheimer's, Parkinson's, Schizophrenia, and a series of inflammatory disorders. In recent years, there has been an increased interest in the pharmacological modulation of receptor function as a therapeutic target. However, these efforts have been limited due to poor temporal and tissue selectivity. Therefore, there is a growing need for the synthesis of new modulators that can address these problems. Positive allosteric modulators (PAMs) for the α7‐nAChR have grown in significance and are currently being developed by many pharmaceutical companies. The California Northstate University has provided us with three novel PAMs (PAM‐2, OCF‐3, CF‐3) in order to test their functionality on the α7‐nAChR. Previous tests on these compounds have shown indirect PAM activity through calcium influx tests using fluorescence microscopy. However, the direct effects of these drugs on the α7‐nAChR have not been tested. Taking advantage of the Xenopus oocyte expression system we are studying the direct effects of these drugs on the α7‐nAChR using Two‐Electrode Voltage Clamp (TEVC) electrophysiology. Our results show that pre‐application of 20 μM PAM‐2, OCF‐3, or CF‐3 on oocytes expressing the α7‐nAChR causes a significant increase in response amplitude compared to controls. Also, we observe a dose dependent increase in current amplitude for PAM‐2 and OCF‐3. These results are consistent with the idea of positive allosteric modulation. Reverse potentials were performed to verify the effects of PAM‐2 and OCF‐3 on calcium permeability of the α7‐nAChR. We have observed that for PAM‐2 the shift in Vrev (ΔVrev) is similar to that of our control. However, for OCF‐3 we observe a reduction in ΔVrev in a low vs high calcium solution. Further studies of these compounds will give us a better insight into their potential use as therapeutic targets of the α7‐nAChR.Support or Funding InformationThis project was funded by the MARC Program at the University of Puerto Rico, Rio Piedras NIGMS Grant #5T34GM007821‐38.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.