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.<ref name="LiebowitzSalman2014">{{cite journal|last1=Liebowitz|first1=Michael R.|last2=Salman|first2=Ester|last3=Nicolini|first3=Humberto|last4=Rosenthal|first4=Norman|last5=Hanover|first5=Rita|last6=Monti|first6=Louis|title=Effect of an Acute Intranasal Aerosol Dose of PH94B on Social and Performance Anxiety in Women With Social Anxiety Disorder|journal=American Journal of Psychiatry|volume=171|issue=6|year=2014|pages=675–682|issn=0002-953X|doi=10.1176/appi.ajp.2014.12101342|url=https://www.researchgate.net/publication/261511611|pmid=24700254|s2cid=38510058 }}</ref><ref name="Monti-BlochJennings-White1994">{{cite journal|last1=Monti-Bloch|first1=L.|last2=Jennings-White|first2=C.|last3=Dolberg|first3=D.S.|last4=Berliner|first4=D.L.|title=The human vomeronasal system|journal=Psychoneuroendocrinology|volume=19|issue=5–7|year=1994|pages=673–686|issn=0306-4530|doi=10.1016/0306-4530(94)90049-3|pmid=7938363|s2cid=36129626 }}</ref><ref name="pmid8836161">{{cite journal | vauthors = Berliner DL, Monti-Bloch L, Jennings-White C, Diaz-Sanchez V | title = The functionality of the human vomeronasal organ (VNO): evidence for steroid receptors | journal = J. Steroid Biochem. Mol. Biol. | volume = 58 | issue = 3 | pages = 259–65 | year = 1996 | pmid = 8836161 | doi = 10.1016/0960-0760(96)00062-3| s2cid = 31206207 }}</ref><ref name="pmid9699878">{{cite journal | vauthors = Monti-Bloch L, Diaz-Sanchez V, Jennings-White C, Berliner DL | title = Modulation of serum testosterone and autonomic function through stimulation of the male human vomeronasal organ (VNO) with pregna-4,20-diene-3,6-dione | journal = J. Steroid Biochem. Mol. Biol. | volume = 65 | issue = 1–6 | pages = 237–42 | year = 1998 | pmid = 9699878 | doi = 10.1016/s0960-0760(98)00025-9}}</ref> Pherines target human chemosensory receptors and possibly other receptors such as the GABA<sub>A</sub> receptor and influence central nervous system activity.<ref name="LiebowitzSalman2014" /><ref name="Monti-BlochJennings-White1994" /><ref name="pmid8836161" /><ref name="pmid9699878" />

Currently known pherine molecules are being developed for the treatment of various medical conditions. Pherines specifically target nasal chemosensory cells<ref name="A">{{cite journal|last1=Monti-Bloch|first1=L|last2=Jennings-White|first2=C|last3=Berliner|first3=DL|title=The human vomeronasal system: a review|journal=Ann NY Acad Sci|date=1988|volume=855|pages=373–89|pmid=9929629|doi=10.1111/j.1749-6632.1998.tb10595.x|s2cid=38973467}}</ref><ref name="B">{{cite journal|last1=Winegar|first1=B|last2=Monti-Bloch|first2=L|title=Vomeropherins produce low-frequency calcium oscillations in human vomeronasal neurons|journal=Chem Senses|date=2003|volume=25th ACHEMS Meeting|issue=Sarasota, FL|page=83}}</ref> and mediate selective modulation of brain areas like the limbic amygdala, hypothalamus, hippocampus, and prefrontal cortex.<ref name="C">{{cite journal|last1=Sobel|first1=N|last2=Prabhakaran|first2=V|author3-link=Catherine Hartley|last3=Hartley|first3=CA|last4=Desmond|first4=JE|author5-link=Gary H. Glover|last5=Glover|first5=GH|last6=Sullivan|first6=EV|author7-link=John Gabrieli|last7=Gabrieli|first7=JD|title=Blind smell: brain activation induced by an undetected air-borne chemical|journal=Brain|date=1999|volume=122|issue=Pt 2|pages=209–17|pmid=10071050|doi=10.1093/brain/122.2.209|doi-access=free}}</ref> 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 <ref name="D">{{cite journal|last1=Freeman|first1=E|last2=Monti-Bloch|first2=L|title=Evaluation of a unique new intranasal aerosol in the treatment of clinically significant premenstrual syndrome|date=2007|volume=47th NCDEU Meeting|issue=Boca Raton, Florida}}</ref><ref name="E">{{cite journal|last1=Liebowitz|first1=MR|last2=Salman|first2=E|last3=Nicolini|first3=H|last4=Rosenthal|first4=N|last5=Hanover|first5=R|last6=Monti|first6=L|title=Effect of an acute intranasal aerosol dose of PH94B on social and performance anxiety in women with social anxiety disorder|journal=Am J Psychiatry|date=2014|volume=171|issue=6|pages=675–82|doi=10.1176/appi.ajp.2014.12101342|pmid=24700254|s2cid=38510058 }}</ref><ref name="F">{{cite journal|last1=Liebowitz|first1=MR|last2=Nicolini|first2=H|last3=Monti|first3=L|last4=Hanover|first4=R|title=PH 10 may be a new rapidly acting intranasally administered antidepressant|date=2013|volume=American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, Miami, Florida}}</ref>

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).<ref name="LiebowitzSalman2014" /><ref name="Monti-BlochJennings-White1994" /><ref name="pmid8836161" /><ref name="pmid9699878" /><ref name="Monti-BlochJennings-White1998">{{cite journal|last1=Monti-Bloch|first1=Louis|last2=Jennings-White|first2=Clive|last3=Berliner|first3=David L.|title=The Human Vomeronasal System: A Review|journal=Annals of the New York Academy of Sciences|volume=855|issue=1 OLFACTION AND|year=1998|pages=373–389|issn=0077-8923|doi=10.1111/j.1749-6632.1998.tb10595.x|pmid=9929629|bibcode=1998NYASA.855..373M |s2cid=38973467 }}</ref> 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.<ref name="E" /><ref name="G">{{cite journal|last1=Liebowitz|first1=M|last2=Monti|first2=L|last3=Hanover|first3=R|last4=Draine|first4=A|title=PH94B nasal spray as a PRN treatment for social anxiety disorder: a phase 3 pilot trial|date=2015|volume=ASCP Annual Meeting|page=T13}}</ref> * PH10 is being developed as an indication for the acute treatment of depression.<ref name="F" /> * 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.<ref name="D" /> * PH15 is in early stage development for the treatment of cognitive impairment.

== See also == * List of neurosteroids

== References == {{Reflist|2}}

Category:Pherines Category:Steroids