AV-101 Mechanism of Action

AV-101's Active Metabolite (7-Cl-KYNA) Does Not Block NMDA Receptor Activity; It Inhibits It

In peer-reviewed, published preclinical studies, AV-101 (4-Cl-KYN) demonstrated robust, rapid-onset and long duration, antidepressant-like activity similar to the NMDA receptor antagonist ketamine hydrochloride, an FDA-approved anesthetic often used off label for treatment resistant major depressive disorder, but without any of ketamine's psychotomimetic and hallucinogenic side effects. In two NIH-funded randomized, double-blind, placebo-controlled Phase 1 safety studies, AV-101 was safe, well-tolerated and not associated with any drug-related severe adverse events. There were no signs of ketamine-like side effects, such as sedation, hallucinations or schizophrenia-like side effects which are often associated with ketamine and other ion channel-blocking NMDA receptor antagonists.

PH94B Mechanism of Action

PH94B was developed from proprietary compounds called pherines. Pherines are synthetic neuroactive steroids that engage nasal chemosensory receptors which, in turn, inhibit nerve circuits mediating behavioral and physiological effects of anxiety. Administered as a nasal spray, PH94B acts locally on peripheral nasal chemosensory receptors that trigger rapid activation of the limbic system areas of the brain associated with social anxiety disorder (SAD). This mechanism of pharmacological action, the rapid onset of efficacy, and the excellent safety and tolerability profile shown in clinical trials make PH94B an excellent product candidate for the acute intermittent and long-term treatment of individuals with SAD.