Deudextromethorphan/quinidine

Deudextromethorphan/quinidine (d-DXM/Q; developmental code names AVP-786, CTP-786) is a combination of deudextromethorphan (d-DXM; deuterated (d6) dextromethorphan (DXM)) and quinidine (Q) which is under development by Avanir Pharmaceuticals for the treatment of a variety of neurological and psychiatric indications.[1][2] The pharmacological profile of d-DXM/Q is similar to that of dextromethorphan/quinidine (DXM/Q).[2] DXM and d-DXM act as σ₁ receptor agonists, NMDA receptor antagonists, and serotonin–norepinephrine reuptake inhibitors, among other actions, while quinidine is an antiarrhythmic agent acting as a CYP2D6 inhibitor.[2] Quinidine inhibits the metabolism of DXM and d-DXM into dextrorphan (DXO), which has a different pharmacological profile from DXM.[2] Deuteration of DXM hinders its metabolism by CYP2D6 into DXO, thereby allowing for lower doses of quinidine in the combination.[2] This in turn allows for lower potential for drug interactions and cardiac adverse effects caused by quinidine.[2] As of September 2020, d-DXM/Q is in phase 3 clinical trials for agitation, phase 2/3 trials for schizophrenia, and phase 2 trials for brain injuries, impulse control disorders, major depressive disorder, and neurodegenerative disorders.[1]