Proof 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
Kantrowitz JT, Grinband J, Goff DC, Lahti AC, Marder SR, Kegeles LS, Girgis RR, Sobeih T, Wall MM, Choo TH, Green MF, Yang YS, Lee J, Horga G, Krystal JH, Potter WZ, Javitt DC, Lieberman JA. Proof 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. Neuropsychopharmacology 2020, 45: 1842-1850. PMID: 32403118, PMCID: PMC7608251, DOI: 10.1038/s41386-020-0706-z.Peer-Reviewed Original ResearchConceptsDorsal anterior cingulate cortexBrief Psychiatric Rating ScaleTS-134Target engagementHealthy volunteersMetabotropic glutamate receptor 2/3 agonistKetamine-induced psychotic symptomsBPRS positive symptomsDouble-blind conditionsProof of mechanismKetamine-induced changesAntipsychotic drug developmentTreatment of schizophreniaPsychiatric Rating ScaleAnterior cingulate cortexPrimary outcomeClinical symptomsGlutamatergic drugsGlutamate neurotransmissionTotal symptomsClinical assessmentLow dosePsychotic symptomsHigh dosePlacebo data