Cycloserine/lurasidone

Cycloserine/lurasidone, developmental code name NRX-101 and tentative brand name Cyclurad, is a combination formulation of the antibiotic D-cycloserine, an antagonist of the glycine site of the NMDA receptor, and lurasidone, an atypical antipsychotic, which is under development by NeuroRx for the treatment of acute suicidal ideation/behavior (ASIB).[1] As of May 2016, it has completed a phase II clinical trial for bipolar depression. In September 2017, the drug received fast track designation for bipolar depression from the United States Food and Drug Administration.[2]

Currently preclinical information on Cyclurad comes from two phase II clinical trials looking at the significance/efficacy of D-cycloserine in the treatment of depression, in which D-cycloserine could be a cost-effective target for novel pharmaceutics (Phase II). There is a clinical trial slated[3] for treatment of ASIB; however, enrollment for the study has not been started as of yet. The investigators will administer an intravenous infusion of ketamine 0.5 mg/kg over 40 minutes, and if the patients respond satisfactory, as deemed by the investigators, then they will be administered a dose Cyclurad or to a comparator group. This clinical trial is in part supported by a letter the editor in the Journal of Clinical Psychiatry, where patients received an acute dose of ketamine, followed by daily D-cycloserine. Patients appeared to show a decrease in depression scores, based Hamilton Depression Rating Scale and Beck Depression Inventory, in the treatment arm.[4] Along with this letter, D-cycloserine was also used in a similar scenario with treatment resistant depression. In this trial, patients were administered either D-cycloserine or a placebo. The main significance of this trial were not just the results from the treatment, but the fact that D-cycloserine, which is an NMDA antagonist, has potential therapeutic role in treating depression.[5]