Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Neurobehavioral Disinhibition Including Aggression, Agitation, and Irritability in Patients With Traumatic Brain Injury
This investigational therapeutic is a deuterated, second-generation version of AVP-923/Nuedexta, a fixed-dose combination of two approved drugs.
Both AVP-923 and AVP-786 contain dextromethorphan, the active ingredient in several brands of cough syrup. Dextromethorphan is a weak antagonist of NMDA receptors, and an agonist of sigma 1 receptors, molecular chaperones located in membranes of the endoplasmic reticulum. Both AVP-923 and AVP-786 also contain quinidine. Otherwise prescribed to treat irregular heartbeat, quinidine in this combination increases the bioavailability of dextromethorphan by slowing its oxidative metabolism by the liver enzyme cytochrome P450-2D6 and by inhibiting the blood-brain barrier protein pump P-glycoprotein.
AVP-786 differs from its predecessor in that it contains deuterium, a naturally occurring, heavier isotope of hydrogen. As developed by Concert Pharmaceuticals, deuterium chemistry leaves a drug’s mechanism of action fundamentally unchanged but can alter its pharmacokinetic properties, for example by slowing its liver metabolism, prolonging exposure in the blood, or reducing its side effect profile.
Avanir engineered AVP-786 together with Concert Pharmaceuticals. In 2014, Otsuka Pharmaceutical Co. acquired Avanir.