Boosting Cognitive Function in Schizophrenia: The Impact of MIN-101 and Metformin
Versacloz® (clozapine, USP) Overview
Versacloz is indicated for treatment-resistant schizophrenia in severely ill patients. Its use is restricted due to significant risks like agranulocytosis and seizures. The effectiveness of clozapine was established in a randomized study comparing it to chlorpromazine in patients who failed other antipsychotic treatments.
Dosing for Versacloz involves a highly concentrated oral suspension where 1 mL equals 50 mg. This method offers a tasteless option, measured and administered with an oral syringe, eliminating the need to mix tablets.
Important safety information includes contraindications for those with hypersensitivity to clozapine or its components. Warnings include potential eosinophilia, QT interval prolongation, and metabolic changes such as hyperglycemia and weight gain. Regular monitoring of glucose levels and weight is essential during treatment.
For support, the Clozapine REMS Program can be contacted at 844-267-8678 or Clozapine REMS.
Cognitive Effects of MIN-101
MIN-101, a combination of sigma-2 and serotonin-2A antagonism, has shown potential in improving cognitive deficits in schizophrenia. This was evaluated in a randomized controlled trial involving 244 participants aged 18 to 60 with moderate to severe negative symptoms. Participants were assigned to receive either placebo, MIN-101 32 mg, or MIN-101 64 mg over a 12-week period.
Results indicated that patients receiving MIN-101 32 mg experienced significant improvements in cognitive performance, as measured by the Brief Assessment of Cognition in Schizophrenia (BACS). Notable enhancements were observed in verbal fluency and composite z scores. The PANSS negative factor scores correlated with cognitive improvements, particularly in the MIN-101 64 mg group.
The trial registered under identifier 2014-004878-42 highlights the need for innovative treatments targeting cognitive impairment in schizophrenia.
Metformin’s Role in Cognitive Improvement
Research indicates that metformin can alleviate cognitive impairment in schizophrenia, particularly when combined with antipsychotic medications. An open-labeled, evaluator-blinded study assigned participants to receive either antipsychotics alone or antipsychotics plus metformin for 24 weeks.
The MATRICS Consensus Cognitive Battery (MCCB) was used to assess cognitive improvements.
Findings revealed that the metformin group exhibited greater enhancements in MCCB composite scores and specific cognitive domains, including working memory and speed of processing. Functional connectivity in the dorsolateral prefrontal cortex (DLPFC) was positively correlated with cognitive performance, suggesting that metformin’s effects are linked to changes in brain connectivity.
The trial is registered under NCT03271866, emphasizing the importance of developing adjunctive treatments for cognitive deficits in schizophrenia.
Iclepertin Development
Iclepertin, developed by Boehringer Ingelheim, is an investigational nootropic aimed at enhancing cognition in schizophrenia. As an inhibitor of glycine transporter 1 (GlyT1), it showed promising results in phase II trials, leading to its advancement into phase III clinical studies.
However, in January 2025, Boehringer Ingelheim announced that the phase 3 program CONNEX did not achieve its primary and secondary endpoints. Patients receiving Iclepertin did not show statistically significant improvements compared to placebo.

The findings from the initial studies of Iclepertin suggest potential for cognitive enhancement in schizophrenia, pending further research.
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