Metoprolol (CED0001823)

Record Information
Version1.0
Creation Date2016-05-22 03:43:38 UTC
Update Date2026-08-19 12:46:38 UTC
Accession NumberCHEM016784
Identification
Common NameMetoprolol
ClassSmall Molecule
Description
Metoprolol is an organic compound with the formula C15H25NO3 and an average molecular weight of 267.36 g/mol. Metoprolol belongs to the tyrosols and derivatives, a subclass of phenols within the organic compounds. It acts as an inhibitor of the Beta-1 adrenergic receptor (ADRB1), Beta-2 adrenergic receptor (ADRB2), and Beta-3 adrenergic receptor (ADRB3). The compound is used as a treatment for high blood pressure (PMC10301436), heart failure (PMC11550835), hypertension (PMC11550835), atrial fibrillation (PMC1492602), arrhythmia (PMC9369816), and pheochromocytoma (PMC10074227). Recorded exposure routes include oral and intravenous administration. Metoprolol is found in or released from 17 recorded sources. Within healthcare, pharmaceuticals, and veterinary products, it is identified as a beta blocking agent. It is also associated with food preservation in the category of food, food processing, and cookware, as well as drinking water and water supply. Other recorded sources include household cleaning and consumer products—specifically bleaching agents, cigar cigarettes, non electric simulated smoking devices, other smoking requisites, and perfumes within detergents and soaps—and electrical and electronic equipment, including antennas, conductors or conductive bodies characterised by the conductive materials, electric hearing aids, electric switches, and electrically stimulated smoking devices.
Contaminant TypeNot Available
Chemical Structure
Synonyms
ValueSource
(RS)-MetoprololChEBI
1-(Isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-olChEBI
(+/-)-metoprololHMDB
BeatrololHMDB
DL-MetoprololHMDB
LopresorHMDB
LopresoreticHMDB
LopressorHMDB, MeSH
MeijoprololHMDB
MetohexalHMDB
Metoprolol succinateHMDB, MeSH
Metoprolol tartrateHMDB, MeSH
MetoprololumHMDB
PreblokHMDB
PresololHMDB
SelokenHMDB, MeSH
SerokenHMDB
SpesicorHMDB, MeSH
Toprol-XLHMDB, MeSH
Beloc durilesMeSH, HMDB
Beloc-durilesMeSH, HMDB
BetalocMeSH, HMDB
Succinate, metoprololMeSH, HMDB
ToprolMeSH, HMDB
BelocDurilesMeSH, HMDB
Betaloc astraMeSH, HMDB
CR-XL, MetoprololMeSH, HMDB
SpesikorMeSH, HMDB
Tartrate, metoprololMeSH, HMDB
Toprol XLMeSH, HMDB
Metoprolol CR-XLMeSH, HMDB
Betaloc-astraMeSH, HMDB
BetalokMeSH, HMDB
Metoprolol CR XLMeSH, HMDB
ToprolXLMeSH, HMDB
BetalocAstraMeSH, HMDB
Chemical FormulaC15H25NO3
Average Molecular Mass267.364 g/mol
Monoisotopic Mass267.183 g/mol
CAS Registry Number51384-51-1
IUPAC Name1-[4-(2-methoxyethyl)phenoxy]-3-[(propan-2-yl)amino]propan-2-ol
Traditional Namemetoprolol
SMILESCOCCC1=CC=C(OCC(O)CNC(C)C)C=C1
InChI IdentifierInChI=1S/C15H25NO3/c1-12(2)16-10-14(17)11-19-15-6-4-13(5-7-15)8-9-18-3/h4-7,12,14,16-17H,8-11H2,1-3H3
InChI KeyIUBSYMUCCVWXPE-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as tyrosols and derivatives. Tyrosols and derivatives are compounds containing a hydroxyethyl group attached to the C4 carbon of a phenol group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenols
Sub ClassTyrosols and derivatives
Direct ParentTyrosols and derivatives
Alternative Parents
Substituents
  • Tyrosol derivative
  • Phenoxy compound
  • Phenol ether
  • Alkyl aryl ether
  • Monocyclic benzene moiety
  • 1,2-aminoalcohol
  • Secondary alcohol
  • Dialkyl ether
  • Secondary amine
  • Secondary aliphatic amine
  • Ether
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Amine
  • Organic oxygen compound
  • Alcohol
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginNot Available
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Organoleptic EffectsNot Available
Physical Properties
StateNot Available
AppearanceNot Available
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.4 g/LALOGPS
logP1.8ALOGPS
logP1.76ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area50.72 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity76.7 m³·mol⁻¹ChemAxon
Polarizability31.9 ųChemAxon
Number of Rings1ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrumsplash10-0udi-7920000000-15359015d85b4c565e86Not AvailableView Spectrum
Predicted GC-MSPredicted GC-MS Spectrumsplash10-00di-9122000000-12f9e089d37951143a41Not AvailableView Spectrum
Predicted GC-MSPredicted GC-MS SpectrumNot AvailableNot AvailableView Spectrum
Predicted GC-MSPredicted GC-MS SpectrumNot AvailableNot AvailableView Spectrum
Predicted GC-MSPredicted GC-MS SpectrumNot AvailableNot AvailableView Spectrum
Predicted GC-MSPredicted GC-MS SpectrumNot AvailableNot AvailableView Spectrum
Predicted GC-MSPredicted GC-MS SpectrumNot AvailableNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0v0c-3248359000-0353ef81c3bc6d7fcfd5Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014l-2514911000-b5f7785723f1eaf61e6fNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-05ir-1729351100-fb362124379cb4616c5eNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-01b9-9760000000-90ea4861dda115391e26Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014l-0920000000-b7c75fc96ea4b12a1f40Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0090000000-5e678ec3b5c3302abb3cNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0190000000-0ea5b7fc1dda907b176bNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-01b9-4940000000-5e4d95fb248589c9af91Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-05gi-4900000000-73204756032f7604c22eNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-05fr-4900000000-597c5d64a09cf1b8f88dNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0zml-5900000000-ca840796f27bfcb3bd0fNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0090000000-9ae9e49826b05fa823f5Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0190000000-cfdea758641b8b5c956eNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-01b9-3940000000-248e03350c5dfe8e1302Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-05gi-4900000000-24d3886dc7605253aeb8Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-05gi-4900000000-08c6d3455af24f523db2Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0zmi-5900000000-9b22afca158afbaeb6d1Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014l-0920000000-851dcbef33e79ed22643Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0090000000-61bef9702ed80c36d107Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00xr-9830000000-19e036f6e7d1698645adNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0ab9-9500000000-a0c8de4980f1bd246201Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00yi-2900000000-bcd2d1e9320ab40c0cbeNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0kn9-3900000000-a4ead9cd3340096bb484Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0970000000-af48fd7b0dbd70f65107Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014l-0920000000-91f6498b9bb55aeeacd9Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-05gi-4900000000-08c6d3455af24f523db2Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0zmi-5900000000-9b22afca158afbaeb6d1Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0090000000-6c8699c935b8f56f29e1Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0090000000-f73decdc321e7d5cf8f2Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0ab9-9500000000-0a283e6c0cf8a953d45aNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00xr-8930000000-c726ae886bc1df7f2653Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0090000000-5e678ec3b5c3302abb3cNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0290000000-f3fa727dba1504d6a616Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00sl-0900000000-8b891f333d6e8268433bNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-001i-0900000000-d1e16724d320e408cb3dNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-053r-0900000000-d476d017c521687ee4f8Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00sl-0900000000-97a653163f676e8cb287Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00xr-9830000000-800dbc8efe909f556f5bNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0090000000-121b4c951b1d4760959fNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0090000000-f323d372fe6d6899db7eNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0ab9-9500000000-b542f4c205208ef4c346Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-01b9-9660000000-0915838fcf2d96ad73d9Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-05fr-4900000000-597c5d64a09cf1b8f88dNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-05gi-4900000000-24d3886dc7605253aeb8Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-01b9-4940000000-96d5b07c0f5e098cdf29Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014l-0920000000-9b3bfbcb37ac9970554bNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0zml-5900000000-ca840796f27bfcb3bd0fNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014l-0920000000-b7c75fc96ea4b12a1f40Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-05gi-4900000000-73204756032f7604c22eNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0090000000-9ae9e49826b05fa823f5Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0190000000-9f81682fff0883289b4fNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-01b9-4940000000-d995917294b1d6f4c292Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014i-0980000000-71eb303c1b145db83d98Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0kn9-3900000000-a4ead9cd3340096bb484Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-014l-0920000000-8471b8a0acd04c3c43b4Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00yi-2900000000-5d36f9011e5041d84b37Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-014i-1290000000-e429d824fc6518e2de0fNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-00xr-9870000000-6859dfe077cd63365e3bNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-00di-9500000000-84deaf041eadbd4d3ea2Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0gb9-1790000000-1fa6e9e32d3d6f058f89Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0udi-1900000000-0545f16ae4bdd137d91eNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0ldr-3900000000-cfffc2daf6eda94b4e60Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-014i-0490000000-c419c6e50a523ef22c2dNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0cdi-2910000000-c67c0baeee553264e7fcNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-014i-0900000000-57e140a742d1b27d554eNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-014i-0090000000-98e8bde9000bacc76f37Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-00xr-9540000000-040ff19068d563928460Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0abc-9200000000-701b7139093aae671acaNot AvailableView Spectrum
Toxicity Profile
Mechanism of ToxicityNot Available
Carcinogenicity (IARC Classification)Not Available
Minimum Risk LevelNot Available
SymptomsNot Available
TreatmentNot Available
Toxicity Values
Toxicity ValueUnitValue RangeOrganismDose DescriptorRoute of ExposurePredicted or ExperimentalReference
1099.0Log mg/kg[620:2000]RatLD50oralpredictedNot Available
Health Effects
Health EffectRelationshipDirectionReference
hypertensionis_treatment_forNot AvailablePMC11550835
heart failureis_treatment_forNot AvailablePMC11550835
high blood pressureis_treatment_forNot AvailablePMC10301436
pheochromocytomais_treatment_forNot AvailablePMC10074227
atrial fibrillationis_treatment_forNot AvailablePMC1492602
arrhythmiais_treatment_forNot AvailablePMC9369816
migraineis_treatment_forNot AvailablePMC12255647
Exposure Sources
Source IDSourceSectorReference
10InsecticidesAgriculture & land managementNot Available
115Drinking waterDrinking water & water supplyNot Available
293Beta blocking agentsHealthcare, pharmaceuticals & veterinary productsNot Available
506AntennasElectrical & Electronic EquipmentNot Available
511Conductors Or Conductive Bodies Characterised By The Conductive MaterialsElectrical & Electronic EquipmentNot Available
516Electric Hearing AidsElectrical & Electronic EquipmentNot Available
517Electric SwitchesElectrical & Electronic EquipmentNot Available
518Electrically Stimulated Smoking DevicesElectrical & Electronic EquipmentNot Available
519ElectrodesElectrical & Electronic EquipmentNot Available
524Hybrid CapacitorsElectrical & Electronic EquipmentNot Available
531RelaysElectrical & Electronic EquipmentNot Available
545Food PreservationFood, food processing & cookwareNot Available
555Bleaching AgentsHousehold cleaning & consumer productsNot Available
556Cigar CigarettesHousehold cleaning & consumer productsNot Available
559Non Electric Simulated Smoking DevicesHousehold cleaning & consumer productsNot Available
560Other Smoking RequisitesHousehold cleaning & consumer productsNot Available
561Perfumes Within Detergents And SoapsHousehold cleaning & consumer productsNot Available
569Tobacco Smoke FiltersHousehold cleaning & consumer productsNot Available
580Manufacture Preparation Of Tobacco ProductsIndustrial manufacturing & chemical processingNot Available
584BuoysMarine, shipping & aquacultureNot Available
596AcaricidesAgriculture & land managementNot Available
600Herbicides And AlgicidesAgriculture & land managementNot Available
605Pest RepellantsAgriculture & land managementNot Available
610Aftersun ProductsPersonal care & cosmeticsNot Available
611Anti Perspirants Or Body DeoderantsPersonal care & cosmeticsNot Available
613DepilatoriesPersonal care & cosmeticsNot Available
614Essential Oils Or PerfumesPersonal care & cosmeticsNot Available
615Eye Makeup ProductsPersonal care & cosmeticsNot Available
617Lip Care ProductsPersonal care & cosmeticsNot Available
618Lip Makeup ProductsPersonal care & cosmeticsNot Available
632ApparelTextiles, leather & furnishingsNot Available
642FootwearTextiles, leather & furnishingsNot Available
653SewingTextiles, leather & furnishingsNot Available
Pathways
3 pathways
Targets
StructureProteinUniProt IDOrganismRelationshipDetails
Click to view 3D structureBeta-1 adrenergic receptorP18090Rattus norvegicusPredicted (SEA)0.311397
Click to view 3D structureBeta-1 adrenergic receptorB0FL73Cavia porcellusPredicted (SEA)0.233548
Click to view 3D structureBeta-2 adrenergic receptorQ8K4Z4Cavia porcellusPredicted (SEA)0.155698
Beta-1 adrenergic receptor structureClick to view 3D structureBeta-1 adrenergic receptorP08588HumansPredicted (SEA)0.233548
Beta-2 adrenergic receptor structureClick to view 3D structureBeta-2 adrenergic receptorP07550HumansPredicted (SEA)0.856341
Click to view 3D structure5-hydroxytryptamine receptor 1AP19327Rattus norvegicusPredicted (SEA)7.39568
Click to view 3D structureBeta-1 adrenergic receptorP34971Mus musculusPredicted (SEA)0.311397
Sigma non-opioid intracellular receptor 1 structureClick to view 3D structureSigma non-opioid intracellular receptor 1Q99720HumansPredicted (SEA)22.0313
Click to view 3D structureBeta-2 adrenergic receptorQ28044Bos taurusPredicted (SEA)1.08989
Beta-3 adrenergic receptor structureClick to view 3D structureBeta-3 adrenergic receptorP13945HumansPredicted (SEA)8.32987
5-hydroxytryptamine receptor 1A structureClick to view 3D structure5-hydroxytryptamine receptor 1AP08908HumansPredicted (SEA)100.893
Cytochrome P450 2D6 structureClick to view 3D structureCytochrome P450 2D6P10635HumansPredicted (SEA)73.7232
Sodium-dependent serotonin transporter structureClick to view 3D structureSodium-dependent serotonin transporterP31645HumansPredicted (SEA)60.3331
Click to view 3D structureBeta-2 adrenergic receptorP10608Rattus norvegicusPredicted (SEA)1.40129
Click to view 3D structureSigma intracellular receptor 2Q5BJF2HumansPredicted (SEA)27.1694
Click to view 3D structureBeta-2 adrenergic receptorP54833Canis lupus familiarisPredicted (SEA)1.08989
Click to view 3D structure5-hydroxytryptamine receptor 1BP28564Rattus norvegicusPredicted (SEA)21.7978
5-hydroxytryptamine receptor 2B structureClick to view 3D structure5-hydroxytryptamine receptor 2BP41595HumansPredicted (SEA)81.9752
5-hydroxytryptamine receptor 2A structureClick to view 3D structure5-hydroxytryptamine receptor 2AP28223HumansPredicted (SEA)170.49
5-hydroxytryptamine receptor 2C structureClick to view 3D structure5-hydroxytryptamine receptor 2CP28335HumansPredicted (SEA)121.912
5-hydroxytryptamine receptor 6 structureClick to view 3D structure5-hydroxytryptamine receptor 6P50406HumansPredicted (SEA)86.1012
Click to view 3D structureDNA (cytosine-5)-methyltransferase 1P13864Mus musculusPredicted (SEA)1.40129
Voltage-gated inwardly rectifying potassium channel KCNH2 structureClick to view 3D structureVoltage-gated inwardly rectifying potassium channel KCNH2Q12809HumansPredicted (SEA)358.729
Extracellular calcium-sensing receptor structureClick to view 3D structureExtracellular calcium-sensing receptorP41180HumansPredicted (SEA)2.64687
5-hydroxytryptamine receptor 1B structureClick to view 3D structure5-hydroxytryptamine receptor 1BP28222HumansPredicted (SEA)80.4182
Concentrations
StatusValueUnitSample LocationReference
External Links
DrugBank IDNot Available
HMDB IDNot Available
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkMetoprolol
Chemspider ID4027
ChEBI ID6904
PubChem Compound ID4171
Kegg Compound IDC07202
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
1. https://www.ncbi.nlm.nih.gov/pubmed/?term=15140634
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=15797646
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=24025984