Metabotropic glutamate (mGlu) receptors are Class C 7-transmembrane domain (7-TMD) G-protein coupled receptors (GPCRs) involved in the modulation of neurotransmission throughout the nervous system [3]. LY2979165 is the alanine prodrug of 2812223, a selective orthosteric mGluR2 agonist. It has been developed with the aim of normalizing aberrant glutamatergic activity in the human brain, and dose-dependently reversed ketamine-evoked increases in glucose metabolism in the rat brain as assayed by 2-deoxyglucose (2-DG) autoradiography [4]. LY2979165 would attenuate the ketamine-evoked BOLD (blood oxygenation level dependent) signal in a dose- and exposure-dependent fashion. A significant mean decrease of 45% in the ketamine-evoked signal at the 60-mg dose of LY2979165 compared to placebo, while the 20-mg dose showed an intermediate level of effect but no statistical separation from placebo. Additionally, pretreatment with LY2979165 dose-dependently augmented the ketamine-induced increases in the cognitive and positive subscales (PANSS), statistically significant (P = 0.008 and P = 0.005, respectively) at the 60-mg dose compared to placebo) [4].
作用机制
LY2979165 is a mGlu2 agonist, a drug candidate drug used to treat bipolar disorder.
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