NN105: An Exploratory Phase II Study to Determine the Tolerability, Safety, and Activity of a Novel Vasopressin 1a Receptor Antagonist (SRX246) in Irritable Subjects with Huntington's Disease (HD)

One such drug is SRX246, a first-in-class vasopressin 1a (V1a) receptor antagonist that crosses the blood-brain barrier following oral administration. The molecule exhibits high affinity and high selectivity for its target receptor, has a strong safety profile, is well-tolerated, and has excellent pharmacokinetics. Preclinical pharmacology studies have demonstrated significant CNS effects in models of irritability, including impulsive aggression, depression, and anxiety. In an experimental medicine fMRI study in healthy volunteers, SRX246 treatment significantly attenuated the effect of intranasal AVP in brain circuits known to modulate emotional responses to stimuli that elicit aggression/fear. Together, these findings suggest that SRX246 has potential as a novel therapeutic agent for major neuropsychiatric symptoms seen in HD patients, and we propose to test its tolerability in such patients when it is given orally at doses up to 160 mg twice daily.