Iclepertin Explained

Legal Status:Investigational
Synonyms:BI 425809
Cas Number:1421936-85-7
Pubchem:155259577
Unii:M43ZDU10DD
C:20
H:18
F:6
N:2
O:5
S:1

Iclepertin (developmental code name BI 425809) is an investigational nootropic to enhance the cognition and functional capacity in schizophrenia developed by Boehringer Ingelheim. 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.[1] Schizophrenia is characterized by abnormalities in glutamatergic pathways related to NMDA receptor hypofunction. Inhibition of GlyT1 on the presynaptic membrane or astrocytes is hypothesized to increase glycine 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.[2]

Notes and References

  1. Fleischhacker WW, Podhorna J, Gröschl M, Hake S, Zhao Y, Huang S, Keefe RS, Desch M, Brenner R, Walling DP, Mantero-Atienza E, Nakagome K, Pollentier S . 6 . Efficacy and safety of the novel glycine transporter inhibitor BI 425809 once daily in patients with schizophrenia: a double-blind, randomised, placebo-controlled phase 2 study . English . The Lancet. Psychiatry . 8 . 3 . 191–201 . March 2021 . 33610228 . 10.1016/S2215-0366(20)30513-7 . 231986987 .
  2. Rosenbrock H, Desch M, Kleiner O, Dorner-Ciossek C, Schmid B, Keller S, Schlecker C, Moschetti V, Goetz S, Liesenfeld KH, Fillon G, Giovannini R, Ramael S, Wunderlich G, Wind S . 6 . Evaluation of Pharmacokinetics and Pharmacodynamics of BI 425809, a Novel GlyT1 Inhibitor: Translational Studies . Clinical and Translational Science . 11 . 6 . 616–623 . November 2018 . 30136756 . 6226115 . 10.1111/cts.12578 .