The Analgesic and Anesthetic Effects of Inhibiting the Interaction of the NMDA Receptor Subunits 2A/2B with Neuronal Nitric Oxide via PDZ Domain of PSD95/SAP90

PSD-95/SAP90 is a molecular scaffold protein that, through interactions involving its PDZ domains, couples the NMDA receptor to cellular signaling pathways at neuronal synapses. PSD-95/SAP90?s mRNA and protein are enriched in the spinal cord and selectively distributed in the superficial dorsal horn, where PSD-95/SAP90 overlapped with the NMDA receptor and neuronal NOS. In spinal cord neurons, PSD-95/SAP90 interacted with the NMDA receptor subunits 2A/2B and neuronal NOS. JHU researchers have determined that disruption of the PSD-95/SAP90-specific coupling of the NMDA receptor to the neuronal NOS has a key role in the mechanisms of analgesia and anesthesia in the spinal cord. The deficiency of PSD-95/SAP90 has a potent antinociceptive action and also has been shown to result in a significant decrease in anesthetic threshold. These actions are not accompanied by side effects on motor function or on the cardiovascular system. Description (Set) Proposed Use (Set) Inhibition of the NMDA receptor-neuronal NOS interaction via PDZ domain linkage of PSD-95/SAP90 is a highly novel approach that will be clinically useful to relieve acute and chronic pain, and to decrease the need for inhalational anesthetics as an adjunct.

Inventor(s): Johns, Roger A.

Type of Offer: Licensing



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