Host: The Japanese Pharmacological Society
Name : The 97th Annual Meeting of the Japanese Pharmacological Society
Number : 97
Location : [in Japanese]
Date : December 14, 2023 - December 16, 2023
The dissociative anesthetics, including phencyclidine (PCP), ketamine and methoxetamine (MXE), are selective and potent NMDA receptor (NMDAR) antagonists that have been reported to cause neurotoxicity, similar to another NMDAR antagonist MK801. Although NMDARs are known to be involved in synaptic transmission and plasticity, the neurotoxic mechanism of dissociative anesthetics remains poorly understood. In the present study, we evaluated the neurotoxicity of PCP, ketamine and MXE using human iPSC-derived neurons. First, we confirmed the expression levels of most NMDAR subunits in human iPSC-derived neurons. Next, we examined the effect of dissociative anesthetics on extracellular field potential using a multielectrode array (MEA) system. Treatment with each dissociative anesthetic decreased the total number of spikes and network bursts in human iPSC-derived neurons. Although we found that exposure to each dissociative anesthetic decreased cell viability in higher dosages, the decrease in total spikes and network bursts occurred at lower doses. These data suggest that dissociative anesthetics induce neurotoxicity by inhibition of the neuronal network activity.
