Fasedienol: A Vomeropherine for Anxiety Treatment

Fasedienol: A Vomeropherine for Anxiety Treatment

Fasedienol (developed under the codes PH94B and Aloradine) is an experimental compound belonging to the vomeropherine class. Designed for administration via nasal spray, this substance is being developed by VistaGen Therapeutics as a "pro re nata" (PRN)—or as-needed—treatment for the acute management of social anxiety disorder. Beyond social anxiety, researchers are investigating its potential efficacy in treating generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD).

Structurally, fasedienol is a positional isomer of androstadienol, a pheromone naturally produced by the body. While it shares similarities with endogenous substances, its specific chemical arrangement is tailored for targeted therapeutic interaction.

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Key Facts

  • Drug Class: Vomeropherine.
  • Administration: Intranasal spray.
  • Primary Target: Acute treatment of social anxiety disorder.
  • Developer: VistaGen Therapeutics.
  • Clinical Status: Failed to show effectiveness in phase 3 clinical trials.
  • Mechanism: Activates human vomeronasal receptor cells at nanomolar concentrations.

Chemical Profile and Identification

Fasedienol, also known as 4-androstadienol or 4,16-androstadien-3β-ol, is characterized by its specific steroid-like structure. Its chemical formula is C19H28O, with a molar mass of 272.432 g·mol. In technical terms, it is identified as (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.

Fasedienol Technical Specifications
Identifier Value
CAS Number 23062-06-8
PubChem CID 9925482
DrugBank ID DB04968
ChemSpider ID 8101117
UNII DTW1NJ7IJH
KEGG ID D12524

Mechanism of Action

Unlike many traditional anxiety medications, fasedienol lacks affinity for standard steroid hormone receptors. Instead, it directly activates isolated human vomeronasal receptor cells—specialized sensory neurons—at nanomolar concentrations, with an EC50 (half maximal effective concentration) of 200 nM.

The Role of GABA A Receptors

Researchers have looked toward related pheromones to understand how fasedienol might work. For example, androstenol acts as a potent positive allosteric modulator of the GABA A receptor, a primary inhibitory neurotransmitter system in the brain that produces anxiolytic (anxiety-reducing) effects in animals.

Other pheromones, such as androstadienol, androstadienone, and androstenone, can be converted into androstenol. Because fasedienol is structurally very similar to androstadienol, it is hypothesized that fasedienol may also be converted into androstenol, potentially contributing to its effects through the potentiation of the GABA A receptor.

Frequently Asked Questions

What is fasedienol used for?

Fasedienol was developed as a nasal spray for the acute treatment of social anxiety disorder, and it has been investigated for the treatment of generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD).

How is fasedienol administered?

It is administered intranasally via a nasal spray formulation.

Does fasedienol act like a steroid hormone?

No, fasedienol lacks affinity for steroid hormone receptors; instead, it targets vomeronasal receptor cells.

What happened during its clinical testing?

Fasedienol failed to demonstrate effectiveness during its phase 3 clinical trials.

What is the relationship between fasedienol and androstenol?

Fasedienol is structurally related to androstadienol. It is hypothesized that it may be converted into androstenol, which is known to modulate GABA A receptors to produce anxiety-reducing effects.

References

  1. "VistaGen Therapeutics Acquires Worldwide License of Phase 3-Ready CNS Drug Candidate from Pherin Pharmaceuticals for As-Needed Treatment of Social Anxiety Disorder :: VistaGen Therapeutics, Inc. (VTGN)". VistaGen Therapeutics, Inc. Archived from the original on 2019-12-19. Retrieved 2019-12-19.
  2. Al Idrus A (13 September 2018). "VistaGen nabs phase 3-ready social anxiety drug from Pherin". FierceBiotech. Retrieved 2019-12-19.
  3. Murphy J (10 December 2019). "FDA Grants Fast Track Designation to PH94B for Treatment of Social Anxiety Disorder". Pharmacy Times. Retrieved 2019-12-19.
  4. Griebel G, Holmes A (September 2013). "50 years of hurdles and hope in anxiolytic drug discovery" (PDF). Nature Reviews. Drug Discovery. 12 (9): 667–87. doi:10.1038/nrd4075. PMC 4176700. PMID 23989795.
  5. Monti-Bloch L, Jennings-White C, Dolberg DS, Berliner DL (1994). "The human vomeronasal system". Psychoneuroendocrinology. 19 (5–7): 673–86. doi:10.1016/0306-4530(94)90049-3. PMID 7938363. S2CID 36129626.