Ketamine binds preferentially to N-methyl-D-aspartate (NMDA) receptors on inhibitory interneurons in the cortex, limbic system (amygdala), and hippocampus, promoting an uncoordinated increase in neural activity, an active electroencephalographic pattern, and unconsciousness, as shown in Panel A. In the spinal cord, ketamine decreases arousal by blocking NMDA glutamate (Glu)–mediated nociceptive signals from peripheral afferent neurons in the dorsal-root ganglion to projecting neurons, as shown in Panel B.