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Ketamine was initially introduced as an anesthetic and analgesic for medical applications ( 5.1 Pharmacological effects 5.1.1 NMDAR antagonism Ketamine exerts its primary effects by acting as a noncompetitive antagonist of NMDARs and reducing glutamate-mediated excitatory neurotransmission ( In animal studies, antagonism of NMDA receptors in intermediate neurons of the forebrain and thalamus reduces GABAergic function