C-10068

C-10068 is a deuterated small-molecule analog of dextroethorphan/(+)-N-methyl-3-ethoxymorphinan, designed by Concert Pharmaceuticals to improve metabolic stability and pharmacokinetics relative to its parent compound while retaining and enhancing central nervous system activity.[1][2][11] Selective replacement of hydrogen with deuterium on the 3-ethoxy and N-methyl groups slows CYP-mediated oxidation, reducing formation of less desirable metabolites and extending systemic exposure.[2][1] Pharmacologically, C-10068 shows complex actions similar to dextromethorphan but with markedly increased affinity for the sigma-1 receptor (approximately sixfold), where it acts as an agonist, and it also modulates glutamatergic and ion-channel–related mechanisms implicated in excitotoxicity.[2][1] In preclinical traumatic brain injury models, continuous intravenous infusion of C-10068 produced robust antiseizure and anti-inflammatory effects, dose-dependently reducing nonconvulsive seizure incidence, frequency, and duration, and attenuating hippocampal astrocyte and microglial activation, with additional evidence of anticonvulsant, neuroprotective, antinociceptive, and antidepressant-like effects in other preclinical evaluations, supporting its exploration for post-traumatic seizures, traumatic brain injury, pain, and mood disorders.[1][2][3][4][7][13][16]

Other names

deuterated dextroethorphandeuterated (+)-N-methyl-3-ethoxymorphinan