LY3027788, a diester analog of LY3020371, an mGlu2/3 receptor antagonist, is a highly potent and orally active prodrug of LY3020371. Notably, LY3027788 exhibits significant antidepressant efficacy.

LY3027788 (4.8-27 mg/kg; a single p.o.) produces antidepressant-like decreases in immobility times in the forced-swim test in mice[1]. LY3027788 (4.8-16 mg/kg; a single p.o.) enhances the locomotor stimulant effects of quinpirole at the dose of 16 mg/kg in the locomotor activity assay in mice[1]. LY3027788 (10-30 mg/kg; a single p.o.) dose dependently increases the wake time of rats without engendering rebound hypersomnolence[1]. LY3027788 (a single p.o.) leads to the rapid and dose-proportionate appearance of the pharmacologically active species LY3020371 in plasma of both mouse (4.8-27 mg/kg) and rat (3-30 mg/kg)[1]. Animal Model: Male Sprague-Dawley mice (20-25 g)[1]Dosage: 4.8, 16, 27 mg/kg Administration: A single p.o. (60 minutes prior to testing) Result: Potent and efficacious with a minimal effective dose of 16 mg/kg in the mouse forced-swim assay. The ED 60 was 8.2 mg/kg.