biostudies-literatureKantrowitz JTNCATS NIH HHSTaisho Toyama Pharmaceutical CompanyNIDA NIH HHSNIMH NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Mental HealthU.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)1842-1850https://www.ebi.ac.uk/biostudies/studies/S-EPMC7608251biostudies-literatureUnknown45(11)Glutamate neurotransmission is a prioritized target for antipsychotic drug development. Two metabotropic glutamate receptor 2/3 (mGluR2/3) agonists (pomaglumetad [POMA] and TS-134) were assessed in two Phase Ib proof of mechanism studies of comparable designs and using identical clinical assessments and pharmacoBOLD methodology. POMA was examined in a randomized controlled trial under double-blind conditions for 10-days at doses of 80 or 320 mg/d POMA versus placebo (1:1:1 ratio). The TS-134 trial was a randomized, single-blind, 6-day study of 20 or 60 mg/d TS-134 versus placebo (5:5:2 ratio). Primary outcomes were ketamine-induced changes in pharmacoBOLD in the dorsal anterior cingulate cortex (dACC) and symptoms reflected on the Brief Psychiatric Rating Scale (BPRS). Both trials were conNeuropsychopharmacology : official publication of the American College of NeuropsychopharmacologyProof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers.PMC7608251HHSN271201200007CU01 MH094247Taisho Pharmaceutical R&D IncFAST-PS contract (HHSN271201200007I)UL1 TR001863Sobeih TGirgis RRGreen MFKegeles LSGoff DCChoo THLee JGrinband JJavitt DCHorga GWall MMKrystal JHYang YSMarder SRLieberman JALahti ACPotter WZKantrowitz JTfalseProof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers.Glutamate neurotransmission is a prioritized target for antipsychotic drug development. Two metabotropic glutamate receptor 2/3 (mGluR2/3) agonists (pomaglumetad [POMA] and TS-134) were assessed in two Phase Ib proof of mechanism studies of comparable designs and using identical clinical assessments and pharmacoBOLD methodology. POMA was examined in a randomized controlled trial under double-blind conditions for 10-days at doses of 80 or 320 mg/d POMA versus placebo (1:1:1 ratio). The TS-134 trial was a randomized, single-blind, 6-day study of 20 or 60 mg/d TS-134 versus placebo (5:5:2 ratio). Primary outcomes were ketamine-induced changes in pharmacoBOLD in the dorsal anterior cingulate cortex (dACC) and symptoms reflected on the Brief Psychiatric Rating Scale (BPRS). Both trials were con2020-01-01T00:00:00Z2020 Oct2026-05-03T04:51:52.727Z2020-11-08T09:45:32ZS-EPMC76082513240311810.1038/s41386-020-0706-z