Effect of PH94B and Steroid Hormones on Nasal Electrogram Responses and Biomarkers of Autonomic Nervous System Activity in Healthy Human Subjects

Abstract: Background and Introduction: PH94B is an investigational pherine nasal spray thought to regulate the olfactory-amygdala circuits of fear and anxiety without direct GABA-A receptor activation or binding to other central nervous system receptors. We compared the effect of PH94B and steroidal hormone administration on the electrogram of the nasal chemosensory mucosa and on biomarkers of autonomic nervous system activity. Methods: In this single-blind study, healthy volunteers (8 men, 8 women) aged 20−60 years randomly received placebo and study drugs (PH94B, estradiol-β, progesterone, cortisol, and testosterone, 0.4 µg each) onto the nasal chemosensory mucosa at 30-minute intervals and electrograms were continuously recorded. Noninvasive electrodes recorded respiratory rate, heart rate, and electrodermal activity 5 minutes before and 15 minutes after intranasal administration. Amplitude and frequency of digitized signals were analyzed using ACQKnowledge software (Biopac Systems); paired comparisons were analyzed using the Student’s t-test. Results: PH94B significantly increased the electrogram amplitude versus placebo, in men (5.0 vs 0.6 mV, P