NMRA-861

NMRA-861 is a highly potent and selective **positive allosteric modulator** (PAM) of the **M4 muscarinic receptor**, currently in Phase 1 clinical development for the treatment of schizophrenia and other neuropsychiatric disorders. NMRA-861 was discovered at the Warren Center for Neuroscience Drug Discovery at Vanderbilt University and is being developed by Neumora Therapeutics. Preclinical studies have demonstrated a **potentially best-in-class pharmacological profile**, robust activity, and a **favorable safety profile** with no observed convulsions in multiple animal models, addressing a limitation seen with other muscarinic modulators. The mechanism of action targets allosteric modulation of the M4 muscarinic receptor, a pathway believed to modulate both cholinergic and dopamine signaling, providing antipsychotic effects without the side effects associated with traditional antipsychotics (such as D2 dopamine receptor blockade). NMRA-861 is being developed as a once-daily oral therapy with the goal of improved tolerability and efficacy for patients with schizophrenia and potentially other neuropsychiatric conditions[1][2][3][4][5][6][7][10].