Iclepertin (developmental code name BI 425809) is an investigational

nootropic Nootropics ( or ) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are chemical substances which purportedly improve cognitive functions, such as attention, memory, wakefulness, and self ...

to enhance the cognition and functional capacity in

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

developed by

Boehringer Ingelheim C.H. Boehringer Sohn AG & Co. is the parent company of the Boehringer Ingelheim group, which was founded in 1885 by Albert Boehringer (1861–1939) in Ingelheim am Rhein, Germany. As of 2018, Boehringer Ingelheim is one of the world's List of la ...

. As of May 2020, it is in phase III of clinical trial under the code name CONNEX-3. BI 425809 is an inhibitor of glycine transporter 1 (Gly-T1) that in phase II improved cognition after 12 weeks in patients with schizophrenia. Doses of 10 mg and 25 mg showed the largest separation from placebo. If these encouraging results are confirmed in phase 3 trials, BI 425809 could provide an effective treatment for cognitive impairment associated with schizophrenia. Schizophrenia is characterized by abnormalities in glutamatergic pathways related to

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...

hypofunction. Inhibition of GlyT1 on the presynaptic membrane or astrocytes is hypothesized to increase

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...

levels within the synapse. The NMDA receptor function may be enhanced by increasing levels of its co-agonist, glycine, within the synaptic cleft, which may lead to improvements in cognitive function. In January 2025, Boehringer Ingelheim announced that the phase 3 program CONNEX missed both the primary and key secondary endpoints. When compared to placebo at six months, patients receiving the Iclepertin drug do not have statistically significant effects in improving cognitive impairment. The laboratory announced stopping a related long-term extension study.

References

Nootropics Experimental drugs developed for schizophrenia Glycine reuptake inhibitors Trifluoromethyl compounds Oxazoles Sulfones Cyclopropyl compounds {{pharma-stub