Refisolone

CAS202718-04-5

MFC18H24O3 MW288.4 g/mol

(1S,2S,4R,6S,7S,10S,11S)-11-hydroxy-7-methyl-5-oxapentacyclo[8.8.0.0^2,7.0^4,6.0^11,16]octadec-15-en-14-one

• (16alpha,17alpha)-16,17-Epoxy-10-hydroxyestr-4-en-3-one
• Estr-4-en-3-one, 16,17-epoxy-10-hydroxy-, (16alpha,17alpha)-

10-hydroxy-16α,17α-epoxyestr-4-en-3-one
GABAA receptor antagonist, migraine. PH 80, 2QA794326X

Refisolone (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name; developmental code names PH-80, Salubrin, and ORG-39479), also known as 10-hydroxy-16α,17α-epoxyestr-4-en-3-one, is a vomeropherine (pherine) which is under development for the treatment of hot flashes, migraine, and premenstrual dysphoric disorder (PMDD).^[1][2][4][3] It is taken intranasally as a nasal spray.^[1][2][3] The pharmacology of refisolone has been studied and reported.^[5][6] The drug is under development by Pherin Pharmaceuticals and VistaGen Therapeutics, with the former having been acquired by the latter in 2023.^[1][2][4][3] As of December 2025, refisolone is in phase 2 clinical trials for all indications.^[1][4] However, a phase 3 trial of refisolone for PMDD is also reported to have been registered in 2015, though its status is listed as unknown.^[3][7]

Refisolone (developmental code name PH-80) is an investigational, non-hormonal pherine (vomeropherine) nasal spray currently in Phase 2 clinical trials for the treatment of menopausal hot flashes (vasomotor symptoms), migraines, and premenstrual dysphoric disorder (PMDD).

Mechanism of Action

Unlike conventional menopausal treatments, Refisolone does not rely on systemic hormone replacement. It is administered intranasally at microgram-level doses to achieve a rapid, on-demand effect. The spray works by activating chemosensory neurons in the nasal cavity, which send signals to the olfactory-limbic and olfactory-hypothalamic pathways in the brain to regulate anxiety and correct body temperature neural circuits.

Current Clinical Status

• FDA Status: The US FDA cleared the Investigational New Drug (IND) application for Refisolone, issuing a “Study May Proceed” letter to allow advanced Phase 2 trials to move forward.
• Development History: The compound was originally created by Pherin Pharmaceuticals, which was fully acquired by Vistagen Therapeutics.
• Clinical Trial Progress: A successful Phase 2a exploratory trial for menopausal hot flashes was completed in Mexico, showing that the compound was well-tolerated with no serious drug-related adverse events.

Intranasal PH80 Spray for Acute Management of the Symptoms of Premenstrual Dysphoric DisorderCTID:

NCT01217775, Phase:Phase 3Status:Unknown status, Date:2015-12-03

PAT

WO2009126825

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2009126825&_cid=P21-MT2BVX-74335-1

The preparation of the estrene compound 16α,17α-epoxy-10β-hydroxyestr-4-en-3-one is described in commonly assigned US Pat. No. 6,057,439, which is incorporated herein by reference. The steroid compound 16α,17α-epoxy-10β-hydroxyestr-4-en-3-one has the chemical structure of:

PAT

WO2025217068

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2025217068&_cid=P21-MT2BVX-74335-2

16a, 17a epoxyestr-4 en-iop ol-3 one will not be associated with or cause endometrial effects such as endometrial hyperplasia or endometrial cancer as are associated with conventional estrogen therapies.

[0054] US Patent No. 6,057,439 (“US 6,057,439) describes the use of a number of steroidal pherines for the treatment of premenstrual dysphoric disorder and anxiety by administration to the vomeronasal organ of an individual suffering from those symptoms. Among the pherines described in U.S. Pat. 6,057,439 is 16a,17a-Epoxyestr-4-en-10|3-ol-3-one, which is also known in the art as PH80, has the following chemical structure:

.S. Pat. 6,057,439 also describes the synthesis of 16a,17a-Epoxyestr-4-en-10p-ol-3-one and pharmaceutical compositions containing it for alleviating symptoms of PMDD. U.S. Pat. 6,331,534 describes the same steroids for alleviating pain by vomeronasal administration. U.S. Pat. 8,431,559, “Treatment of hot flashes”, describes a synthesis of 16a,17a-epoxyestr-4-en-10p-ol-3-one, which it refers to as 16a,17a-epoxy-10p-hydroxyestr-4-en-3-one, and a method of using 16a,17a-epoxyestr-4-en-10p-ol-3-one to alleviating hot flashes by administering 16a,17a-epoxyestr-4-en-10p-ol-3-one via intranasal administration. U.S.

Pat. 11,419,881, “Treatment of migraine”, similarly describes a synthesis of 16a,17a-epoxyestr-4-en-10P-ol-3-one and also refers to the drug as 16a,17a-epoxy-10p-hydroxyestr-4-en-3-one. U.S. Pat. 11,419,881 also describes a method for alleviating migraines by nasally administering 16a,17a-epoxyestr-4-en-10p-ol-3-one .

PAT

• Treatment of migrainePublication Number:US-2020323884-A1Priority Date:2019-04-15
• Treatment of migrainePublication Number:EP-3955933-A1Priority Date:2019-04-15
• Treatment of migrainePublication Number:EP-3955933-B1Priority Date:2019-04-15Grant Date:2023-11-29
• Treatment of migrainePublication Number:WO-2020214452-A1Priority Date:2019-04-15
• Steroid treatment for hot flashesPublication Number:US-2009258040-A1Priority Date:2008-04-09
• Treatment of Hot FlashesPublication Number:US-2012108558-A1Priority Date:2008-04-09
• Steroid treatment for hot flashesPublication Number:WO-2009126825-A1Priority Date:2008-04-09
• Steroid treatment for hot flashesPublication Number:EP-2278880-A1Priority Date:2008-04-09
• Treatment of hot flashesPublication Number:US-8431559-B2Priority Date:2008-04-09Grant Date:2013-04-30
• Steroid treatment for hot flashesPublication Number:EP-2278880-B1Priority Date:2008-04-09Grant Date:2012-10-10
• Steroids as neurochemical stimulators of the vno to alleviate symptoms of pmsPublication Number:EP-0914165-B1Priority Date:1996-07-23Grant Date:2006-10-18
• Steroids as neurochemical stimulators of the VNO to alleviate symptoms of PMS and anxietyPublication Number:US-6057439-APriority Date:1994-08-04Grant Date:2000-05-02
• Steroids as neurochemical stimulators of the VNO to treat paroxistic tachycardiaPublication Number:US-6117860-APriority Date:1994-08-04Grant Date:2000-09-12
• Steroids as neurochemical stimulators of the VNO to alleviate painPublication Number:US-6331534-B1Priority Date:1994-08-04Grant Date:2001-12-18

ADVERISEMENT

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References

References

1.  “VistaGen Therapeutics”. AdisInsight. Springer Nature Switzerland AG. 2 December 2025. Retrieved 9 March 2026.
2.  “Pherin Pharmaceuticals”. AdisInsight. Springer Nature Switzerland AG. 28 July 2024. Retrieved 9 March 2026.
3.  “PH-80 Drug Profile”. Ozmosi. Retrieved 9 March 2026.
4.  “Delving into the Latest Updates on Refisolone”. Synapse. PatSnap. 28 February 2026. Retrieved 9 March 2026.
5.  Monti L, Baker RA, Hanover R (25 November 2025). Refisolone PH80 Nasal Spray Effects on In Vitro Receptor Binding, Reproductive Organs in Mice, and Pharmacokinetic Profile in Humans. The Menopause Society 2025 Annual Meeting.
6.  Monti L, Baker RA, Hanover R (25 November 2025). Refisolone PH80 Nasal Spray Effects on Brain and Autonomic Activity: A Novel, Investigational, Rapid-Onset Non-Hormonal Treatment for Vasomotor Symptoms Due to Menopause. The Menopause Society 2025 Annual Meeting.
7.  Clinical trial number NCT01217775 for “Intranasal PH80 Spray for Acute Management of the Symptoms of Premenstrual Dysphoric Disorder (PH80-PMD)” at ClinicalTrials.gov

External links

• Refisolone (PH80) – Vistagen Therapeutics

Clinical data
Other names	PH-80; PH80; PH-80-M; PH80-M; PH80M; PH80-PMD NS; PH80-HF; PH80-HF NS; Salubrin; Salubrin HF; ORG-39479; ORG39479; 10-Hydroxy-16α,17α-epoxyestr-4-en-3-one; 16α,17α-Epoxyestr-4-en-10-ol-3-one
Routes of administration	Intranasal (nasal spray)[1][2][3]
Drug class	Vomeropherine
Identifiers
IUPAC name
CAS Number	202718-04-5
PubChem CID	21968346
UNII	2QA794326X
Chemical and physical data
Formula	C18H24O3
Molar mass	288.387 g·mol−1
3D model (JSmol)	Interactive image
SMILES
InChI

//////////refisolone, anax labs, GABAA receptor antagonist, migraine. PH 80, 2QA794326X