Obstructive Sleep Apnoea (OSA) — RepurpOS

Disease overview

Alterations

108

Molecular (A)

100

Clinical (B–E)

Direct drugs

114

Via biomarker

126

Natural agents

Natural products

Merged ranked

237

With trial/literature evidence

Sources: Open Targets, HPO, ClinicalTrials.gov, DGIdb, ChEMBL, PubMed Literature, Examine.com, disease_db_100 · Pipeline phase 7 · Updated 2026-07-06

Remission & chronicity

Spontaneous remission

Spontaneous resolution without intervention rare; weight loss of 10-15% reduces AHI by 25-50% in obese patients; mild OSA may resolve with weight loss; moderate-severe OSA essentially irreversible without intervention

Best-intervention remission

CPAP: eliminates apnoeic events (AHI <5) in 95%+ when used; improves BP 2-3 mmHg, Epworth sleepiness, QoL; mandibular advancement device (MAD): reduces AHI 50-60% in mild-moderate, less effective in severe; bariatric surgery: AHI reduction 80-85% (OSA resolution in 40-50%); hypoglossal nerve stimulation (Inspire): AHI reduction 68% at 12 months

Drug-free remission

—

Relapse after remission

—

Chronicity

—

Gap size

Very large — CPAP adherence is the dominant problem; 30-50% of CPAP-prescribed patients are non-adherent; alternative approaches (MAD, positional therapy, weight loss) underused in non-adherent patients

Primary barrier

practice/adherence

Barrier detail: CPAP adherence is the single largest challenge in sleep medicine; 50% of patients discontinue CPAP within 1-3 years; inadequate follow-up support and lack of alternatives to CPAP for non-adherent patients; hypoglossal nerve stimulation (Inspire) is highly effective in CPAP-intolerant patients but vastly underutilised

Last SoC change: 2024 — tirzepatide showing 60-70% AHI reduction in obese OSA patients (SURMOUNT-OSA trial); 2023 Inspire (HNS) expanded indications; 2014 Inspire FDA approved; CPAP as standard since 1981; essentially unchanged paradigm for 40 years in most clinical settings

Remission data layers: disease_db_100 · source-locked manual data · confidence: high

Identifiers: MONDO: MONDO:0007147 · ORPHA: ORPHA:1713

Right to Try Relevance

Eligibility: This disease meets the federal and state right-to-try legal standard (21 U.S.C. § 360bbb-0a and Montana SB 535): it lacks disease-modifying therapy with indication-specific FDA approval. Patients with Obstructive Sleep Apnea may be eligible to access investigational therapies outside of clinical trials under right-to-try frameworks.

Investigational Agents

Phase 3: 22, Phase 2: 18

Most Advanced Phase

Phase 3

Highest dev. stage

Gene Targets

108

Actionable

Pipeline Compounds (Top 6)

Amiloride, Amlodipine, Aroxybutynin, Atomoxetine, Budesonide, Chlorthalidone

Legal Standard: Right-to-try requires the disease lacks "adequate approved therapy for that specific disease" (not symptom-management drugs). This distinction means a disease with antidepressants available still qualifies if no FDA approval exists for THAT disease indication.

View Right-to-Try Compendium

Alterations

Showing 80 of 108 · Types A (molecular) through E (functional)

Name	Type	Subtype	Direction	Frequency	Evidence	Sources	Links
Anosmia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Excessive daytime somnolence	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Focal impaired awareness seizure	Functional	Functional test	—	—	Moderate	HPO, Monarch	HPO
Obstructive sleep apnea	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Snoring	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
ADAMTS17 ADAM metallopeptidase with thrombospondin type 1 motif 17	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ALDH1A2 aldehyde dehydrogenase 1 family member A2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
APOE apolipoprotein E	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
AUTS2 activator of transcription and developmental regulator AUTS2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Apnea Hypopnea Index	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
BMP5 bone morphogenetic protein 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1C calcium voltage-gated channel subunit alpha1 C	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1D calcium voltage-gated channel subunit alpha1 D	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1F calcium voltage-gated channel subunit alpha1 F	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA1S calcium voltage-gated channel subunit alpha1 S	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CADM2 cell adhesion molecule 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CCDC77 coiled-coil domain containing 77	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CYSLTR1 cysteinyl leukotriene receptor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
EPB41L4A erythrocyte membrane protein band 4.1 like 4A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ETV5 ETS variant transcription factor 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
EVI5 ecotropic viral integration site 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FANCL FA complementation group L	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FTO FTO alpha-ketoglutarate dependent dioxygenase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Fatigue Severity Scale	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
GABRA1 gamma-aminobutyric acid type A receptor subunit alpha1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA2 gamma-aminobutyric acid type A receptor subunit alpha2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA3 gamma-aminobutyric acid type A receptor subunit alpha3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA4 gamma-aminobutyric acid type A receptor subunit alpha4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA5 gamma-aminobutyric acid type A receptor subunit alpha5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRA6 gamma-aminobutyric acid type A receptor subunit alpha6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRB1 gamma-aminobutyric acid type A receptor subunit beta1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRB2 gamma-aminobutyric acid type A receptor subunit beta2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRB3 gamma-aminobutyric acid type A receptor subunit beta3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRD gamma-aminobutyric acid type A receptor subunit delta	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRE gamma-aminobutyric acid type A receptor subunit epsilon	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRG1 gamma-aminobutyric acid type A receptor subunit gamma1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRG2 gamma-aminobutyric acid type A receptor subunit gamma2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRG3 gamma-aminobutyric acid type A receptor subunit gamma3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRP gamma-aminobutyric acid type A receptor subunit pi	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GABRQ gamma-aminobutyric acid type A receptor subunit theta	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GAPVD1 GTPase activating protein and VPS9 domains 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GIPR gastric inhibitory polypeptide receptor	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GLP1R glucagon like peptide 1 receptor	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GNPDA2 glucosamine-6-phosphate deaminase 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GPD2 glycerol-3-phosphate dehydrogenase 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
HRH3 histamine receptor H3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
KCNA3 potassium voltage-gated channel subfamily A member 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
KCNK3 potassium two pore domain channel subfamily K member 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
KIF18A kinesin family member 18A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
LHX8 LIM homeobox 8	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
LRMDA leucine rich melanocyte differentiation associated	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MAD1L1 mitotic arrest deficient 1 like 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MDFIC MyoD family inhibitor domain containing	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MSRB3 methionine sulfoxide reductase B3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
N4BP2 NEDD4 binding protein 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
NR3C1 nuclear receptor subfamily 3 group C member 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
NRP1 neuropilin 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
NRXN3 neurexin 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
OGN osteoglycin	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
OLFM4 olfactomedin 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
OTX2 orthodenticle homeobox 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PAP Adherence (TIME versus Standard of Care)	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
PCSK1 proprotein convertase subtilisin/kexin type 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDE11A phosphodiesterase 11A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDZRN4 PDZ domain containing ring finger 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PRIM1 DNA primase subunit 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PRUNE2 prune homolog 2 with BCH domain	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PTBP2 polypyrimidine tract binding protein 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
R3HDM1 R3H domain containing 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
RCC1L RCC1 like	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
RNPEP arginyl aminopeptidase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
RSPO3 R-spondin 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCAPER S-phase cyclin A associated protein in the ER	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN10A sodium voltage-gated channel alpha subunit 10	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN11A sodium voltage-gated channel alpha subunit 11	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN1A sodium voltage-gated channel alpha subunit 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN2A sodium voltage-gated channel alpha subunit 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN3A sodium voltage-gated channel alpha subunit 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN4A sodium voltage-gated channel alpha subunit 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
SCN5A sodium voltage-gated channel alpha subunit 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets

FDA-Approved Therapies

Phase 4 agents with regulatory approval for this indication

Drug Name	Mechanism	Type
ACETAZOLAMIDE	None	Gene-targeted
ADUCANUMAB		Gene-targeted
AMLODIPINE BENZOATE	blocker	Gene-targeted
AMLODIPINE BESYLATE	blocker	Gene-targeted
AMLODIPINE BESYLATE		Gene-targeted
AMLODIPINE MALEATE	blocker	Gene-targeted
AMPHETAMINE	None	Gene-targeted
APIXABAN		Gene-targeted
ATENOLOL		Gene-targeted
ATORVASTATIN		Gene-targeted
BEPRIDIL HYDROCHLORIDE	blocker	Gene-targeted
BICALUTAMIDE	None	Gene-targeted
BUPROPION HYDROCHLORIDE		Gene-targeted
CAFFEINE		Gene-targeted
CAPECITABINE		Gene-targeted
CARBACHOL	None	Gene-targeted
CELECOXIB		Gene-targeted
CHOLESTEROL		Gene-targeted
CHORIOGONADOTROPIN ALFA		Gene-targeted
CINNARIZINE	blocker	Gene-targeted
CIPROFLOXACIN	None	Gene-targeted
CITALOPRAM		Gene-targeted
CLEVIDIPINE	blocker	Gene-targeted
CLOMIPRAMINE	None	Gene-targeted
DEHYDRATED ALCOHOL		Gene-targeted
DESFLURANE		Gene-targeted
DIAZEPAM	None	Gene-targeted
DICHLORPHENAMIDE	None	Gene-targeted
DIETHYLSTILBESTROL	None	Gene-targeted
DILTIAZEM HYDROCHLORIDE	blocker	Gene-targeted
DILTIAZEM MALATE	blocker	Gene-targeted
DONANEMAB		Gene-targeted
DONEPEZIL		Gene-targeted
DRONEDARONE HYDROCHLORIDE	blocker	Gene-targeted
ENFLURANE		Gene-targeted
EPIRUBICIN	None	Gene-targeted
ETHOXZOLAMIDE	None	Gene-targeted
FELODIPINE	blocker	Gene-targeted
FENOFIBRATE MICRONIZED		Gene-targeted
FLUMAZENIL	None	Gene-targeted

Therapeutics

Direct disease associations, biomarker-linked drugs, OSMF narrative-review natural agents, and merged ranking. Only agents with registry trials or published clinical literature are shown by default.

Show agents without direct trial evidence

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
ACETAZOLAMIDE	Small molecule	Approved	Strong	100	8 trials 4 Trial pubs 3 RCT View evidence Registry trials NCT07635563 — DReAMzz- Dronabinol and Acetazolamide Medication for Sleep Apnea (ZZ). Dose Confirmation Crossover Study for IHL-42X in Subjects With Obstructive Sleep Apnea. (NOT_YET_RECRUITING) PHASE2 NCT05293600 — Rescue Pharmacotherapy for OSA (RECRUITING) PHASE1, PHASE2 NCT00108602 — Sleep Apnea: Mechanism and Cerebrovascular Consequences (WITHDRAWN) NA NCT01499485 — Treatment of Metabolic Alkalosis With Acetazolamide. Effect on the Length of Mechanical Ventilation. (COMPLETED) PHASE3 NCT06146101 — RePOSA-Revealing the Efficacy of IHL-42X Use in Patients With OSA (ACTIVE_NOT_RECRUITING) PHASE2, PHASE3 NCT05804084 — Patient-centered and Neurocognitive Outcomes With Acetazolamide for Sleep Apnea (RECRUITING) PHASE2 NCT06776432 — Safety and Efficacy Study of Sivopixant, Acetazolamide and SASS-001 in Sleep Apnea (ACTIVE_NOT_RECRUITING) PHASE2 NCT05857384 — Bioavailability, Bioequivalence and Tolerability of IHL-42X Compared to the Reference Drugs (COMPLETED) PHASE1 Published literature Clinical trial publication Impact of acetazolamide and CPAP on cortical activity in obstructive sleep apnea patients (PloS one, 2014) Clinical trial publication Effect of acetazolamide and autoCPAP therapy on breathing disturbances among patients with obstructive sleep apnea syndrome who travel to altitude: a randomized controlled trial (JAMA, 2012) Clinical trial publication Patients with obstructive sleep apnea syndrome benefit from acetazolamide during an altitude sojourn: a randomized, placebo-controlled, double-blind trial (Chest, 2012) Clinical trial publication [Treatment of obstructive sleep apnea syndrome with a mandibular positioning device and other nonsurgical modalities] (Nihon Kyobu Shikkan Gakkai zasshi, 1995) CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
INDOMETHACIN	Small molecule	Approved	Strong	100	4 trials View evidence Registry trials NCT05074056 — Ketorolac on Postoperative Pain Reduction in Pediatric Patients with Adenotonsillectomy (COMPLETED) PHASE4 NCT03467750 — Effect of Ketorolac on Post Adenotonsillectomy Pain (COMPLETED) PHASE4 NCT04483427 — Multimodal Postoperative Analgesia Following OSA Surgery (UNKNOWN) NA NCT01280006 — Effect of Selective and Nonselective Cyclooxygenase Enzyme Inhibition on Arterial Blood Pressure and Cerebral Blood Flow With Exposure to Intermittent Hypoxia in Humans (COMPLETED) PHASE1, PHASE2 CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
METOPROLOL	Small molecule	Approved	Strong	100	No indexed hits View evidence CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ADUCANUMAB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMLODIPINE BENZOATE Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
AMLODIPINE BESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
AMLODIPINE BESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMLODIPINE MALEATE Repurposing	Small molecule	Approved	Strong	95	2 trials View evidence Registry trials NCT01896661 — Effect of Antihypertensive Agents Over Sleep Apnea (COMPLETED) PHASE3 NCT02058823 — Intermittent Hypoxia 2: Cardiovascular and Metabolism (TERMINATED) PHASE4 CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
AMPHETAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
APIXABAN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATENOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATORVASTATIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BEPRIDIL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
BICALUTAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
BUPROPION HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CAFFEINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CAPECITABINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CARBACHOL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CELECOXIB Repurposing	Small molecule	Approved	Strong	95	1 trials View evidence Registry trials NCT01280006 — Effect of Selective and Nonselective Cyclooxygenase Enzyme Inhibition on Arterial Blood Pressure and Cerebral Blood Flow With Exposure to Intermittent Hypoxia in Humans (COMPLETED) PHASE1, PHASE2 CT.gov search · Cochrane · PubMed	DGIdb	—
CHOLESTEROL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CHORIOGONADOTROPIN ALFA Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CINNARIZINE Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
CIPROFLOXACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CITALOPRAM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CLEVIDIPINE Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
CLOMIPRAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DEHYDRATED ALCOHOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DESFLURANE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DIAZEPAM Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DICHLORPHENAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIETHYLSTILBESTROL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DILTIAZEM HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
DILTIAZEM MALATE Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
DONANEMAB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DONEPEZIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DRONEDARONE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
ENFLURANE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
EPIRUBICIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ETHOXZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
FELODIPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
FENOFIBRATE MICRONIZED Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
FLUMAZENIL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
FLUVASTATIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
GABAPENTIN Repurposing	Small molecule	Approved	Strong	95	2 trials View evidence Registry trials NCT00886236 — Study of the Effect of the Drug Gabapentin on Postoperative Pain and Incidence of Postoperative Nausea and Vomiting (COMPLETED) NA NCT02987985 — Efficacy of Opioid-free Anesthesia in Reducing Postoperative Respiratory Depression in Children Undergoing Tonsillectomy (COMPLETED) PHASE3 CT.gov search · Cochrane · PubMed	DGIdb	—
GABAPENTIN ENACARBIL Repurposing	Small molecule	Approved	Strong	95	2 trials View evidence Registry trials NCT00886236 — Study of the Effect of the Drug Gabapentin on Postoperative Pain and Incidence of Postoperative Nausea and Vomiting (COMPLETED) NA NCT02987985 — Efficacy of Opioid-free Anesthesia in Reducing Postoperative Respiratory Depression in Children Undergoing Tonsillectomy (COMPLETED) PHASE3 CT.gov search · Cochrane · PubMed	DGIdb	—
GALANTAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
GANCICLOVIR Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
HALOPERIDOL DECANOATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
HALOTHANE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
HYDROCHLOROTHIAZIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
AMILORIDE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
AMLODIPINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
AROXYBUTYNIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ATOMOXETINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
BUDESONIDE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
CHLORTHALIDONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
CHOLECALCIFEROL	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
DAPAGLIFLOZIN	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
DEXAMETHASONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ECNOGLUTIDE	Biologic	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ELORALINTIDE	Biologic	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ESZOPICLONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
FLUTICASONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LEVOTHYROXINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
LIDOCAINE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
MARIDEBART CAFRAGLUTIDE	Biologic	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
MAZDUTIDE	Biologic	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
MOMETASONE FUROATE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
MONTELUKAST	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ORFORGLIPRON	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
TIRZEPATIDE	Biologic	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ZOPICLONE	Small molecule	Phase III	Moderate	80	—	Open Targets	ChEMBL Open Targets
ACETAZOLAMIDE	Small molecule	Phase II	Emerging	60	8 trials 4 Trial pubs 3 RCT View evidence Registry trials NCT07635563 — DReAMzz- Dronabinol and Acetazolamide Medication for Sleep Apnea (ZZ). Dose Confirmation Crossover Study for IHL-42X in Subjects With Obstructive Sleep Apnea. (NOT_YET_RECRUITING) PHASE2 NCT05293600 — Rescue Pharmacotherapy for OSA (RECRUITING) PHASE1, PHASE2 NCT00108602 — Sleep Apnea: Mechanism and Cerebrovascular Consequences (WITHDRAWN) NA NCT01499485 — Treatment of Metabolic Alkalosis With Acetazolamide. Effect on the Length of Mechanical Ventilation. (COMPLETED) PHASE3 NCT06146101 — RePOSA-Revealing the Efficacy of IHL-42X Use in Patients With OSA (ACTIVE_NOT_RECRUITING) PHASE2, PHASE3 NCT05804084 — Patient-centered and Neurocognitive Outcomes With Acetazolamide for Sleep Apnea (RECRUITING) PHASE2 NCT06776432 — Safety and Efficacy Study of Sivopixant, Acetazolamide and SASS-001 in Sleep Apnea (ACTIVE_NOT_RECRUITING) PHASE2 NCT05857384 — Bioavailability, Bioequivalence and Tolerability of IHL-42X Compared to the Reference Drugs (COMPLETED) PHASE1 Published literature Clinical trial publication Impact of acetazolamide and CPAP on cortical activity in obstructive sleep apnea patients (PloS one, 2014) Clinical trial publication Effect of acetazolamide and autoCPAP therapy on breathing disturbances among patients with obstructive sleep apnea syndrome who travel to altitude: a randomized controlled trial (JAMA, 2012) Clinical trial publication Patients with obstructive sleep apnea syndrome benefit from acetazolamide during an altitude sojourn: a randomized, placebo-controlled, double-blind trial (Chest, 2012) Clinical trial publication [Treatment of obstructive sleep apnea syndrome with a mandibular positioning device and other nonsurgical modalities] (Nihon Kyobu Shikkan Gakkai zasshi, 1995) CT.gov search · Cochrane · PubMed	Open Targets	ChEMBL Open Targets
ALLOPURINOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
APREPITANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ATORVASTATIN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BOSENTAN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
BOTULINUM TOXIN TYPE A	Biologic	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
CAFFEINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DANAVOREXTON	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DESIPRAMINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DEXMEDETOMIDINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DIMETHYL FUMARATE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
DRONABINOL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
ERGOCALCIFEROL	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
KETAMINE	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LEMBOREXANT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LIPOIC ACID, ALPHA	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LORUNDROSTAT	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets
LOSARTAN	Small molecule	Phase II	Emerging	60	—	Open Targets	ChEMBL Open Targets

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
ACETAZOLAMIDE Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	8 trials 4 Trial pubs 3 RCT View evidence Registry trials NCT07635563 — DReAMzz- Dronabinol and Acetazolamide Medication for Sleep Apnea (ZZ). Dose Confirmation Crossover Study for IHL-42X in Subjects With Obstructive Sleep Apnea. (NOT_YET_RECRUITING) PHASE2 NCT05293600 — Rescue Pharmacotherapy for OSA (RECRUITING) PHASE1, PHASE2 NCT00108602 — Sleep Apnea: Mechanism and Cerebrovascular Consequences (WITHDRAWN) NA NCT01499485 — Treatment of Metabolic Alkalosis With Acetazolamide. Effect on the Length of Mechanical Ventilation. (COMPLETED) PHASE3 NCT06146101 — RePOSA-Revealing the Efficacy of IHL-42X Use in Patients With OSA (ACTIVE_NOT_RECRUITING) PHASE2, PHASE3 NCT05804084 — Patient-centered and Neurocognitive Outcomes With Acetazolamide for Sleep Apnea (RECRUITING) PHASE2 NCT06776432 — Safety and Efficacy Study of Sivopixant, Acetazolamide and SASS-001 in Sleep Apnea (ACTIVE_NOT_RECRUITING) PHASE2 NCT05857384 — Bioavailability, Bioequivalence and Tolerability of IHL-42X Compared to the Reference Drugs (COMPLETED) PHASE1 Published literature Clinical trial publication Impact of acetazolamide and CPAP on cortical activity in obstructive sleep apnea patients (PloS one, 2014) Clinical trial publication Effect of acetazolamide and autoCPAP therapy on breathing disturbances among patients with obstructive sleep apnea syndrome who travel to altitude: a randomized controlled trial (JAMA, 2012) Clinical trial publication Patients with obstructive sleep apnea syndrome benefit from acetazolamide during an altitude sojourn: a randomized, placebo-controlled, double-blind trial (Chest, 2012) Clinical trial publication [Treatment of obstructive sleep apnea syndrome with a mandibular positioning device and other nonsurgical modalities] (Nihon Kyobu Shikkan Gakkai zasshi, 1995) CT.gov search · Cochrane · PubMed	ChEMBL	ChEMBL Open Targets
ADUCANUMAB Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
AMLODIPINE BENZOATE Repurposing via CACNA1F	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
AMLODIPINE BESYLATE Repurposing via CACNA1F	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
AMLODIPINE BESYLATE Repurposing via CACNA1C	Small molecule	Approved	Strong	95	—	DGIdb	—
AMLODIPINE MALEATE Repurposing via CACNA1F	Small molecule	Approved	Strong	95	2 trials View evidence Registry trials NCT01896661 — Effect of Antihypertensive Agents Over Sleep Apnea (COMPLETED) PHASE3 NCT02058823 — Intermittent Hypoxia 2: Cardiovascular and Metabolism (TERMINATED) PHASE4 CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
AMPHETAMINE Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
APIXABAN Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
ATENOLOL Repurposing via CACNA1C	Small molecule	Approved	Strong	95	—	DGIdb	—
ATORVASTATIN Repurposing via CACNA1S	Small molecule	Approved	Strong	95	—	DGIdb	—
BEPRIDIL HYDROCHLORIDE Repurposing via CACNA1F	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
BICALUTAMIDE Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
BUPROPION HYDROCHLORIDE Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
CAFFEINE Repurposing via CACNA1S	Small molecule	Approved	Strong	95	—	DGIdb	—
CAPECITABINE Repurposing via CCDC77	Small molecule	Approved	Strong	95	—	DGIdb	—
CARBACHOL Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CELECOXIB Repurposing via CACNA1F	Small molecule	Approved	Strong	95	1 trials View evidence Registry trials NCT01280006 — Effect of Selective and Nonselective Cyclooxygenase Enzyme Inhibition on Arterial Blood Pressure and Cerebral Blood Flow With Exposure to Intermittent Hypoxia in Humans (COMPLETED) PHASE1, PHASE2 CT.gov search · Cochrane · PubMed	DGIdb	—
CHOLESTEROL Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
CHORIOGONADOTROPIN ALFA Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
CINNARIZINE Repurposing via CACNA1F	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
CIPROFLOXACIN Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CITALOPRAM Repurposing via CACNA1C	Small molecule	Approved	Strong	95	—	DGIdb	—
CLEVIDIPINE Repurposing via CACNA1F	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
CLOMIPRAMINE Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DEHYDRATED ALCOHOL Repurposing via CADM2	Small molecule	Approved	Strong	95	—	DGIdb	—
DESFLURANE Repurposing via CACNA1S	Small molecule	Approved	Strong	95	—	DGIdb	—
DIAZEPAM Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DICHLORPHENAMIDE Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DIETHYLSTILBESTROL Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DILTIAZEM HYDROCHLORIDE Repurposing via CACNA1F	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
DILTIAZEM MALATE Repurposing via CACNA1F	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
DONANEMAB Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
DONEPEZIL Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
DRONEDARONE HYDROCHLORIDE Repurposing via CACNA1F	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
ENFLURANE Repurposing via CACNA1S	Small molecule	Approved	Strong	95	—	DGIdb	—
EPIRUBICIN Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ETHOXZOLAMIDE Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
FELODIPINE Repurposing via CACNA1F	Small molecule	Approved	Strong	95	—	DGIdb	—
FENOFIBRATE MICRONIZED Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
FLUMAZENIL Repurposing via ALDH1A2	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets

Natural Products

11 natural products with the same evidence schema as repurposed drugs — registry trials, PubMed literature, and reference links (pipeline-ranked). Only agents with direct clinical evidence are shown by default.

Reference lookups: Examine.com

Show agents without direct trial evidence

Drug	Type	Phase	Evidence	Score	Trials & literature	Links
Magnesium Natural product Human Study Low levels of magnesium were associated with a higher CRP concentration…	Nutraceutical	Preclinical	Emerging	10	2 trials View evidence Registry trials NCT05678439 — Effects of Sesamin on Sleep Quality and Antioxidative Status (COMPLETED) NA NCT04621032 — Obstructive Sleep Apnea Destabilizes Myocardial Repolarization Homogeneity (COMPLETED) CT.gov search · Cochrane · PubMed	PubChem
Vitamin D3 Natural product Human Study This study provides evidence that serum 25-hydrpoxyvitamin D and obstru…	Nutraceutical	Phase III	Emerging	10	3 trials View evidence Registry trials NCT01323218 — Sleep Apnea Syndrome and Vitamin D (UNKNOWN) PHASE2 NCT06690723 — Vitamin D and SGLT-2 Inhibitor in CPAP-naive Obstructive Sleep Apnea (COMPLETED) PHASE3 NCT05232201 — Vitamin D Levels and Heart Rate Variability on Endothelial Function Via RAAS Augmentation in OSA (UNKNOWN) CT.gov search · Cochrane · PubMed	PubChem
Melatonin Natural product Clinical trial publication Circadian rhythms in blood pressure, heart rate, hormones, and on polys… Human Study Melatonin mediates intestinal barrier dysfunction and systemic inflamma…	Nutraceutical	Approved	Emerging	7	3 trials 1 Trial pubs View evidence Registry trials NCT02484300 — The Effect of Melatonin on Sleep and Ventilatory Control in Obstructive Sleep Apnea (COMPLETED) NA NCT06380491 — Melatonin's Effect on Nighttime Blood Pressure and Sleep in OSA Patients (MEBP-OSA) (RECRUITING) PHASE4 NCT03492736 — Effects of Melatonin in Untreated Obstructive Sleep Apnea (TERMINATED) EARLY_PHASE1 Published literature Clinical trial publication Circadian rhythms in blood pressure, heart rate, hormones, and on polysomnographic parameters in severe obstructive sleep apnea syndrome patients: effect of continuous positive airway pressure (Blood pressure monitoring, 2016) CT.gov search · Cochrane · PubMed	PubChem
L-Citrulline Natural product Animal Study Citrulline might represent a new pharmacological strategy in OSA patien…	Amino acid	Preclinical	Emerging	7	No indexed hits View evidence CT.gov search · Cochrane · PubMed	PubChem
Lactobacillus Natural product Animal Study Lactobacillus rhamnosus GG strain mitigated the development of obstruct…	Probiotic	Preclinical	Emerging	7	No indexed hits View evidence CT.gov search · Cochrane · PubMed	—
Astragaloside Natural product Animal Study Astragaloside IV attenuates chronic intermittent hypoxia-induced myocar…	Nutraceutical	Preclinical	Emerging	0	2 pubs View evidence CT.gov search · Cochrane · PubMed	—
Honokiol Natural product Animal Study, In Vitro Study Honokiol protects pancreatic β cell against high glucose and intermitte…	Nutraceutical	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	—
Paeoniflorin Natural product Animal Study Paeoniflorin could be a novel strategy for hypoxia-induced brain injury.	Nutraceutical	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	—
Flavonoids Natural product Animal Study, In Vitro Study Pinocembrin can act as a potential therapeutic strategy for intermitten…	Nutraceutical	Preclinical	Emerging	0	1 pubs View evidence CT.gov search · Cochrane · PubMed	—
Sesamol Natural product Animal Study Sesamol alleviates chronic intermittent hypoxia-induced cognitive defic…	Nutraceutical	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	—
Tanshinone Iia Natural product In Vitro Study Tanshinone IIA inhibited intermittent hypoxia induced neuronal injury t…	Nutraceutical	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	—

Alterations and therapeutics are aggregated from public databases (Open Targets, HPO, ChEMBL, DGIdb, and others). Natural agents are candidates from OSMF narrative reviews on opensourcemed.info/chronic-disease.html — not approved treatments. This page is for research orientation only — not medical advice.