Pomaglumetad Effects on Glutamate Biomarkers

This study evaluates the effects of POMA at selected doses on ketamine-stimulated glutamate
increase in the prefrontal cortex hypothesized to simulate the synaptic dysregulation that
occurs endogenously in the pathogenesis of schizophrenia. The purpose of this is: 1) to
determine whether the low dose (40 mg BID) utilized in recent (failed) clinical trials is
sufficient to engage the primary target and 2) whether a higher (160 mg BID) dose,
representing the maximum tolerated dose of POMA, engages the target to a greater degree. This
study will further validate pharmacoBOLD as biomarker of mGluR2/3 target engagement,
permitting its future use in other glutamatergic drug development.

Inclusion Criteria:

- Medically healthy

- Capable of understanding the study procedures and able to provide informed consent

- Men and women must agree to use a reliable method of birth control during the study.
Women who are post-menopausal or otherwise not of childbearing potential are also
eligible

Exclusion Criteria:

- Current or past Axis I psychiatric history

- Positive urine toxicology

- History of recreational ketamine use, recreational PCP use, or an adverse reaction to
ketamine. Subjects who have participated in prior research ketamine studies will be
eligible. Subjects can have infusions not more frequently than biweekly, and not more
than 1/month on average, therefore subjects entering the study will need to wait one
month if they had a single infusion and 6 weeks if they have had two closely spaced
infusions.

- History of first-degree relative with schizophrenia

- History of violence

- Presence or positive history of significant medical illness

- Presence or positive history neurological illness or any other
disease/procedure/accident/intervention association with significant injury to or
malfunction of the central nervous system (CNS) or history of significant head injury

- Pregnancy or breast feeding

- Metal implants, pacemaker, other metal or paramagnetic objects contained within the
body

- Medicinal patch, unless removed prior to MRI scan

- Currently taking any psychotropic medication, including antidepressant medications,
benzodiazepines, antipsychotic medications, mood stabilizers, anti-epileptic
medications and stimulants.

- Claustrophobia

- Suicidal ideation with intent or plan in the 6 months prior to screening

- Weight > 86.95 kg (191.2 lbs)

- Subthreshold pharmacoBOLD response during screening ketamine infusion