4,16-Androstadien-3β-ol

4,16-Androstadien-3β-ol
Systematic (IUPAC) name
(3S,8S,9S,10R,13R,14S)-10,13-Dimethyl-2,3,6,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol
Clinical data
Routes of
administration		 Intranasal
Identifiers
CAS Number 23062-06-8
ATC code None
PubChem CID 9925482
DrugBank DB04968
ChemSpider 8101117
Synonyms 3β-Androsta-4,16-dien-3-ol, androsta-4,16-dien-3β-ol, androstadienol
Chemical data
Formula C19H28O
Molar mass 272.43 g·mol−1

4,16-Androstadien-3β-ol (developmental code name PH94B; tentative commercial name Aloradine or Aloradine IN) is a pherine which is under development by Pherin Pharmaceuticals, Inc. in a nasal spray formulation for the acute (p.r.n.) treatment of social anxiety disorder in women.[1][2][3][4][5][6][7][8] It is also being investigated by Pherin Pharmaceuticals for the treatment of generalized anxiety disorder in women.[2] As of 2015, it is in phase III clinical trials.[9]

The compound lacks affinity for steroid hormone receptors and has instead been found to directly activate isolated human vomeronasal receptor cells at nanomolar concentrations (EC50 = 200 nM).[6]

The pheromone androstenol has been found to act as a potent positive allosteric modulator of the GABAA receptor, and it has been proposed that this action may mediate its pheromone effects.[10] It produces anxiolytic-like effects in animals.[10] Androstadienol, androstadienone, and androstenone, all of which are also pheromones, have been found to be converted into androstenol, and as such, it may be responsible for their pheromone effects.[10] As 4,16-androstadien-3β-ol is very closely related structurally to androstadienol (which is 5,16-androstadien-3β-ol), being a positional isomer of the steroid, the mechanism of action of 4,16-androstadien-3β-ol could similarly be potentiation of the GABAA receptor.[10]

See also

References

  1. ↑ Laird Harrison (11 April 2014). "Could a New Nasal Spray Help Combat Social Anxiety?". Healthline. Retrieved 23 May 2015.
  2. 1 2 Griebel, Guy; Holmes, Andrew (2013). "50 years of hurdles and hope in anxiolytic drug discovery" (PDF). Nature Reviews Drug Discovery 12 (9): 667–687. doi:10.1038/nrd4075. ISSN 1474-1776. PMID 23989795.
  3. ↑ 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.
  4. ↑ Edmund T. Rolls (November 2013). Emotion and Decision Making Explained. Oxford University Press. pp. 356–. ISBN 978-0-19-965989-0.
  5. ↑ BioScan. Oryx Press. 2009.
  6. 1 2 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" (PDF). American Journal of Psychiatry 171 (6): 675–682. doi:10.1176/appi.ajp.2014.12101342. ISSN 0002-953X. PMID 24700254.
  7. ↑ http://ascpmeeting.org/wp-content/uploads/2014/05/ASCP-Poster-Abstract-Book-Online.pdf
  8. ↑ US patent 8722652, Louis Monti-Bloch, "Acute Treatment of Social Phobia", published 13 November 2012, assigned to Pherin Pharmaceuticals, Inc.
  9. ↑ http://www.pherin.com/products.html
  10. 1 2 3 4 Kaminski, R. M. (2006). "The Pheromone Androstenol (5 -Androst-16-en-3 -ol) Is a Neurosteroid Positive Modulator of GABAA Receptors". Journal of Pharmacology and Experimental Therapeutics 317 (2): 694–703. doi:10.1124/jpet.105.098319. ISSN 0022-3565.

External links


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