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Ketamine67HOW KETAMINE WORKS IN THE BRAINOne of the major neurotransmitters in the brain is an aminoacid called glutamate. When neurons secrete glutamate onto aneighboring nerve cell, that neighboring nerve cell becomesactivated and passes along the electrical signal to other regionsof the brain. Glutamate can activate several types of receptorson nerve cells, and one of the primary subtypes of glutamatereceptors is called the N-methyl-D-aspartate (NMDA) receptor.When NMDA receptors are inhibited or “blocked” by certaindrugs, nerve cells in the brain that use glutamate as a neurotransmittercannot communicate properly.Ketamine acts as a blocker (or “antagonist”) of the NMDAreceptor. PCP also acts as an antagonist of the NMDA receptor,as does alcohol, although much less potently. NMDA receptorsare present in numerous brain regions, and ketamine isthought to produce its effects by blocking NMDA receptors ina number of brain regions, as shown in Table 6.1.Table 6.1 Ketamine’s Effect on the BrainEFFECTDistorted thoughts, vision,and hearingDizzinessDifficulty moving, impairedcoordinationNumbnessAmnesiaAltered breathing,heart rateBRAIN REGION(S)Frontal cortex, visualcortexFrontal cortex, brainstemMotor cortex, basalganglia, cerebellumSpinal cord, sensorycortexHippocampus(limbic system)Brainstem