Pherine

Pherines, also known as vomeropherines, are odorless synthetic neuroactive steroids that engage nasal chemosensory receptors and induce dose-dependent and reversible pharmacological and behavioral effects.^[1]^[2]^[3]^[4] Pherines target human chemosensory receptors and possibly other receptors such as the GABA_A receptor and influence central nervous system activity.^[1]^[2]^[3]^[4]

Currently known pherine molecules are being developed for the treatment of various medical conditions. Pherines specifically target nasal chemosensory cells^[5]^[6] and mediate selective modulation of brain areas like the limbic amygdala, hypothalamus, hippocampus, and prefrontal cortex.^[7] In clinical trials, pherines formulated for intranasal administration in ultra low doses (nanogram to low microgram quantities) showed rapid onset of efficacy (10–15 minutes) and an excellent safety and tolerability profile. Pherines are also minimally invasive (do not require systemic absorption) to exert their pharmacological effects and can be used on demand ^[8]^[9]^[10]

Pherines described in the scientific literature include PH10, PH15, PH80, PH284 and fasedienol (PH94B, Aloradine, or 4,16-androstadien-3β-ol, a positional isomer of androstadienol).^[1]^[2]^[3]^[4]^[11] Pherines are chemically and pharmacologically different from natural pheromones including androstadienone, androstenone, androstenol, androsterone, and estratetraenol.

Examples of pherines

Fasedienol (PH94B; Aloradine; 4,16-androstadien-3β-ol) is an investigational new drug proposed for the acute treatment of social anxiety disorder.^[9]^[12]
PH10 is being developed as an indication for the acute treatment of depression.^[10]
PH80. In clinical trials this pherine molecule showed efficacy to relieve premenstrual symptoms and it is also being studied for its beneficial effect to reduce menopausal hot flashes.^[8]
PH15 is in early stage development for the treatment of cognitive impairment.

References

^ ^a ^b ^c Liebowitz, Michael R.; Salman, Ester; Nicolini, Humberto; Rosenthal, Norman; Hanover, Rita; Monti, Louis (2014). "Effect of an Acute Intranasal Aerosol Dose of PH94B on Social and Performance Anxiety in Women With Social Anxiety Disorder". American Journal of Psychiatry. 171 (6): 675–682. doi:10.1176/appi.ajp.2014.12101342. ISSN 0002-953X. PMID 24700254. S2CID 38510058.
^ ^a ^b ^c Monti-Bloch, L.; Jennings-White, C.; Dolberg, D.S.; Berliner, D.L. (1994). "The human vomeronasal system". Psychoneuroendocrinology. 19 (5–7): 673–686. doi:10.1016/0306-4530(94)90049-3. ISSN 0306-4530. PMID 7938363. S2CID 36129626.
^ ^a ^b ^c Berliner DL, Monti-Bloch L, Jennings-White C, Diaz-Sanchez V (1996). "The functionality of the human vomeronasal organ (VNO): evidence for steroid receptors". J. Steroid Biochem. Mol. Biol. 58 (3): 259–65. doi:10.1016/0960-0760(96)00062-3. PMID 8836161. S2CID 31206207.
^ ^a ^b ^c Monti-Bloch L, Diaz-Sanchez V, Jennings-White C, Berliner DL (1998). "Modulation of serum testosterone and autonomic function through stimulation of the male human vomeronasal organ (VNO) with pregna-4,20-diene-3,6-dione". J. Steroid Biochem. Mol. Biol. 65 (1–6): 237–42. doi:10.1016/s0960-0760(98)00025-9. PMID 9699878.
^ Monti-Bloch, L; Jennings-White, C; Berliner, DL (1988). "The human vomeronasal system: a review". Ann NY Acad Sci. 855: 373–89. doi:10.1111/j.1749-6632.1998.tb10595.x. PMID 9929629. S2CID 38973467.
^ Winegar, B; Monti-Bloch, L (2003). "Vomeropherins produce low-frequency calcium oscillations in human vomeronasal neurons". Chem Senses. 25th ACHEMS Meeting (Sarasota, FL): 83.
^ Sobel, N; Prabhakaran, V; Hartley, CA; Desmond, JE; Glover, GH; Sullivan, EV; Gabrieli, JD (1999). "Blind smell: brain activation induced by an undetected air-borne chemical". Brain. 122 (Pt 2): 209–17. doi:10.1093/brain/122.2.209. PMID 10071050.
^ ^a ^b Freeman, E; Monti-Bloch, L (2007). "Evaluation of a unique new intranasal aerosol in the treatment of clinically significant premenstrual syndrome". 47th NCDEU Meeting (Boca Raton, Florida). {{cite journal}}: Cite journal requires |journal= (help)
^ ^a ^b Liebowitz, MR; Salman, E; Nicolini, H; Rosenthal, N; Hanover, R; Monti, L (2014). "Effect of an acute intranasal aerosol dose of PH94B on social and performance anxiety in women with social anxiety disorder". Am J Psychiatry. 171 (6): 675–82. doi:10.1176/appi.ajp.2014.12101342. PMID 24700254. S2CID 38510058.
^ ^a ^b Liebowitz, MR; Nicolini, H; Monti, L; Hanover, R (2013). "PH 10 may be a new rapidly acting intranasally administered antidepressant". American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, Miami, Florida. {{cite journal}}: Cite journal requires |journal= (help)
^ Monti-Bloch, Louis; Jennings-White, Clive; Berliner, David L. (1998). "The Human Vomeronasal System: A Review". Annals of the New York Academy of Sciences. 855 (1 OLFACTION AND): 373–389. Bibcode:1998NYASA.855..373M. doi:10.1111/j.1749-6632.1998.tb10595.x. ISSN 0077-8923. PMID 9929629. S2CID 38973467.
^ Liebowitz, M; Monti, L; Hanover, R; Draine, A (2015). "PH94B nasal spray as a PRN treatment for social anxiety disorder: a phase 3 pilot trial". ASCP Annual Meeting: T13. {{cite journal}}: Cite journal requires |journal= (help)