Aptinyx Inc. announced that data from preclinical studies evaluating NYX-783, a novel NMDA receptor positive allosteric modulator, in models of post-traumatic stress disorder were published in the journal, Molecular Psychiatry. The publication, entitled "Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear," details the ability of NYX-783 to reduce fear-based behaviors in animal models of PTSD by measuring enhanced fear extinction and reduced spontaneous recovery of fear. NYX-783 significantly reduced spontaneous recovery of fear in mice in the conventional auditory fear-conditioning model.

NYX-783 also reduced spontaneous recovery in the single-prolonged stress model of PTSD. These data suggest NYX-783 can inhibit the spontaneous recovery of learned fear even after exposure to an additional significant stressor. The inhibition of spontaneous recovery of learned fear by NYX-783 results from increased NMDAR2B-mediated activity of neurons in the infralimbic medial prefrontal cortex.

These results elucidate the cellular targets of NYX-783 and the molecular mechanisms underlying the inhibition of spontaneous recovery. These preclinical findings indicate NYX-783 may be particularly useful for inhibiting spontaneous recovery of fear and provide further support for the drug candidate's therapeutic potential as a treatment for PTSD. The study was led by Boyoung Lee, Ph.D., of the Center for Cognition and Sociality at the Institute for Basic Science, Republic of Korea, while working with the late Ronald Duman, Ph.D., at the Department of Psychiatry, Yale School of Medicine.