Onfasprodil  (Synonyms: MIJ-821)

Onfasprodil (MIJ-821) is a selective intravenous NMDA receptor NR2B subunit negative allosteric modulator (NAM). Onfasprodil inhibits the activity of NR2B-NMDA receptors. Onfasprodil has a rapid antidepressant effect. Onfasprodil can be used for the research of treatment-resistant depression (TRD)^[1][2].

N-Methyl-d-aspartate (NMDA) receptors are widely expressed in the mammalian central nervous system (CNS). Activation of the NMDA receptors depends on the simultaneous binding of two co-agonists: glutamate and either glycine or d-serine. Glutamate binds to the GluN2 subunits, and binding of glycine to the GluN1 subunit results in activation via the opening of the channel pore and subsequently causes the flow of ions through NMDA receptors. Functionally, NMDA receptors mediate excitatory synaptic transmission and plasticity by allowing the flux of calcium ions into neurons. NMDA-dependent synaptic plasticity is essential for many types of learning and memory formation. Dysfunction of NMDA receptors has been implicated in many neurological and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, neuropathic pain, stroke, brain trauma, schizophrenia, and depression.

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358.41

C₂₀H₂₃FN₂O₃

1892581-29-1

O[C@H](C1=CC=C(C=N1)O)CN(C2)C[C@](C3)([H])[C@@]2([H])C[C@H]3OC4=C(C=CC=C4)F

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Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Gomez-Mancilla B, et al. MIJ821 (onfasprodil) in healthy volunteers: First-in-human, randomized, placebo-controlled study (single ascending dose and repeated intravenous dose). Clin Transl Sci. 2023;16(11):2236-2252.  [Content Brief]

  [2]. Shelton RC, et al. Rapid Onset and Sustained Efficacy of Onfasprodil (MIJ821), a Novel NR2B Negative Allosteric Modulator, in Patients With Treatment-Resistant Depression: A Phase 2, Randomized, Placebo-Controlled, Proof-of-Concept Study. J Clin Psychiatry. 2025 Aug 6;86(3):23m15246.  [Content Brief]