Group II metabotropic glutamate receptor agonist prodrugs LY2979165 and LY2140023 attenuate the functional imaging response to ketamine in healthy subjects

Background Aberrant glutamate neurotransmission, and in particular dysfunction of the N-methyl-d-aspartate receptor (NMDAR), has been implicated in psychiatric disorders and represents a novel therapeutic target. Low-dose administration of the NMDA antagonist ketamine in healthy volunteers elicits a strong blood oxygenation level dependent (BOLD) imaging signal that can be attenuated by pretreatment with single, therapeutically effective doses of marketed medicines interacting with the glutamate system.