LY3027788 hydrochloride is a diester analog of LY3020371, a selective antagonist of the metabotropic glutamate 2 and 3 receptors (mGlu2/3). It serves as a highly potent and orally bioavailable prodrug of LY3020371. Notably, LY3027788 hydrochloride exhibits antidepressant efficacy.

LY3027788 administered orally at single doses ranging from 4.8 to 27 mg/kg demonstrably induces antidepressant-like effects by reducing immobility times in the forced-swim test in mice, and at doses between 4.8 and 16 mg/kg, it amplifies the locomotor stimulant effects of quinpirole (16 mg/kg) in a locomotor activity assay in mice. Additionally, at doses from 10 to 30 mg/kg, LY3027788 dose-dependently prolongs wakefulness in rats without causing subsequent excessive sleepiness. Furthermore, a single oral dose of LY3027788 ensures the rapid and dose-proportional presence of the active metabolite LY3020371 in the plasma of both mice (4.8-27 mg/kg) and rats (3-30 mg/kg).

LY3027788, when administered orally at doses ranging from 4.8 to 27 mg/kg, significantly reduces immobility times in mice during the forced-swim test, indicating antidepressant-like effects. At doses between 4.8 and 16 mg/kg, it also amplifies the locomotor stimulant effects of quinpirole in mice, particularly noticeable at a quinpirole dose of 16 mg/kg. Furthermore, administering LY3027788 in doses from 10 to 30 mg/kg increases wakefulness in rats, without causing subsequent hypersomnolence. Additionally, a single oral dose leads to a rapid and dose-dependent increase in the concentration of LY3020371, its active metabolite, in the plasma of both mice (4.8-27 mg/kg) and rats (3-30 mg/kg). In SPN Model using male Sprague-Dawley mice weighing 20-25 g, a single oral dose 60 minutes before testing revealed LY3027788 to be potent and efficacious, with a minimal effective dose of 16 mg/kg in the forced-swim assay and an ED_60 of 8.2 mg/kg.