NMRA-266

NMRA-266 is a highly selective positive allosteric modulator (PAM) of the M4 muscarinic receptor, developed by Neumora Therapeutics for the treatment of schizophrenia and other neuropsychiatric disorders. The drug was discovered at Vanderbilt University and licensed to Neumora. By selectively targeting the M4 receptor subtype in the brain, NMRA-266 aims to modulate dopamine neurotransmission, which is implicated in both positive and negative symptoms as well as cognitive deficits associated with schizophrenia. This mechanism offers potential antipsychotic efficacy while minimizing side effects commonly seen with non-selective muscarinic agonists or current antipsychotics. Preclinical studies demonstrated high potency and selectivity for M4, but a Phase 1 clinical trial was placed on hold by the FDA due to convulsions observed in rabbits during preclinical safety testing; no such events were reported in human participants dosed so far[1][2][4][5][6][8][9].