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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2022-03-07 02:51:44 UTC
HMDB IDHMDB0014750
Secondary Accession Numbers
  • HMDB14750
Metabolite Identification
Common NameBisoprolol
DescriptionBisoprolol is a cardioselective β1-adrenergic blocking agent used for secondary prevention of myocardial infarction (MI), heart failure, angina pectoris and mild to moderate hypertension. Bisoprolol is structurally similar to metoprolol, acebutolol and atenolol in that it has two substituents in the para position of the benzene ring. The β1-selectivity of these agents is thought to be due in part to the large substituents in the para position. At lower doses (less than 20 mg daily), bisoprolol selectively blocks cardiac β1-adrenergic receptors with little activity against β2-adrenergic receptors of the lungs and vascular smooth muscle. Receptor selectivity decreases with daily doses of 20 mg or greater. Unlike propranolol and pindolol, bisoprolol does not exhibit membrane-stabilizing or sympathomimetic activity. Bisoprolol possesses a single chiral centre and is administered as a racemic mixture. Only l-bisoprolol exhibits significant β-blocking activity.
Structure
Data?1582753217
Synonyms
ValueSource
(+-)-1-((alpha-(2-Isopropoxyethoxy)-p-tolyl)oxy)-3-(isopropylamino)-2-propanolChEBI
(RS)-1-(4-(2-Isopropoxyethoxymethyl)phenoxy)-3-(isopropylamino)-2-propanolChEBI
BisoprololumChEBI
(+-)-1-((a-(2-Isopropoxyethoxy)-p-tolyl)oxy)-3-(isopropylamino)-2-propanolGenerator
(+-)-1-((Α-(2-isopropoxyethoxy)-p-tolyl)oxy)-3-(isopropylamino)-2-propanolGenerator
Bisoprolol fumarateHMDB
Bisoprolol fumerateHMDB
Bisoprolol hemifumarateHMDB
Bisoprolol fumarate (2:1) salt, (+-)-isomerMeSH, HMDB
Bisoprolol, (-)-isomerMeSH, HMDB
Bisoprolol, fumarate (1:1) saltMeSH, HMDB
Merck brand OF bisoprolol fumarateMeSH, HMDB
Bisoprolol hydrochlorideMeSH, HMDB
Bisoprolol, (+-)-isomerMeSH, HMDB
Bisoprolol, fumarate (2:1) saltMeSH, HMDB
Fumarate, bisoprololMeSH, HMDB
Bisoprolol fumarate (1:1) salt, (+-)-isomerMeSH, HMDB
Bisoprolol methanesulfonate saltMeSH, HMDB
ConcorMeSH, HMDB
Hydrochloride, bisoprololMeSH, HMDB
Chemical FormulaC18H31NO4
Average Molecular Weight325.443
Monoisotopic Molecular Weight325.225308485
IUPAC Name1-[(propan-2-yl)amino]-3-(4-{[2-(propan-2-yloxy)ethoxy]methyl}phenoxy)propan-2-ol
Traditional Name1-{4-[(2-isopropoxyethoxy)methyl]phenoxy}-3-(isopropylamino)propan-2-ol
CAS Registry Number66722-44-9
SMILES
CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1
InChI Identifier
InChI=1S/C18H31NO4/c1-14(2)19-11-17(20)13-23-18-7-5-16(6-8-18)12-21-9-10-22-15(3)4/h5-8,14-15,17,19-20H,9-13H2,1-4H3
InChI KeyVHYCDWMUTMEGQY-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzylethers
Direct ParentBenzylethers
Alternative Parents
Substituents
  • Benzylether
  • Phenoxy compound
  • Phenol ether
  • Alkyl aryl ether
  • 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
Ontology
Physiological effectNot Available
Disposition
Process
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point100 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.071 g/LNot Available
LogP2.2Not Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M+H]+CBM192.230932474
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.071 g/LALOGPS
logP2.3ALOGPS
logP2.2ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area59.95 ŲChemAxon
Rotatable Bond Count12ChemAxon
Refractivity92.15 m³·mol⁻¹ChemAxon
Polarizability38.5 ųChemAxon
Number of Rings1ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+177.62431661259
DarkChem[M-H]-176.49231661259
DeepCCS[M+H]+186.22230932474
DeepCCS[M-H]-183.86430932474
DeepCCS[M-2H]-216.75130932474
DeepCCS[M+Na]+192.31530932474
AllCCS[M+H]+184.032859911
AllCCS[M+H-H2O]+181.332859911
AllCCS[M+NH4]+186.432859911
AllCCS[M+Na]+187.132859911
AllCCS[M-H]-180.232859911
AllCCS[M+Na-2H]-181.332859911
AllCCS[M+HCOO]-182.732859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
BisoprololCC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C12841.6Standard polar33892256
BisoprololCC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C12316.0Standard non polar33892256
BisoprololCC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C12320.9Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Bisoprolol,1TMS,isomer #1CC(C)NCC(COC1=CC=C(COCCOC(C)C)C=C1)O[Si](C)(C)C2364.0Semi standard non polar33892256
Bisoprolol,1TMS,isomer #2CC(C)OCCOCC1=CC=C(OCC(O)CN(C(C)C)[Si](C)(C)C)C=C12518.6Semi standard non polar33892256
Bisoprolol,2TMS,isomer #1CC(C)OCCOCC1=CC=C(OCC(CN(C(C)C)[Si](C)(C)C)O[Si](C)(C)C)C=C12541.3Semi standard non polar33892256
Bisoprolol,2TMS,isomer #1CC(C)OCCOCC1=CC=C(OCC(CN(C(C)C)[Si](C)(C)C)O[Si](C)(C)C)C=C12465.9Standard non polar33892256
Bisoprolol,2TMS,isomer #1CC(C)OCCOCC1=CC=C(OCC(CN(C(C)C)[Si](C)(C)C)O[Si](C)(C)C)C=C12772.7Standard polar33892256
Bisoprolol,1TBDMS,isomer #1CC(C)NCC(COC1=CC=C(COCCOC(C)C)C=C1)O[Si](C)(C)C(C)(C)C2576.9Semi standard non polar33892256
Bisoprolol,1TBDMS,isomer #2CC(C)OCCOCC1=CC=C(OCC(O)CN(C(C)C)[Si](C)(C)C(C)(C)C)C=C12762.7Semi standard non polar33892256
Bisoprolol,2TBDMS,isomer #1CC(C)OCCOCC1=CC=C(OCC(CN(C(C)C)[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C)C=C12998.6Semi standard non polar33892256
Bisoprolol,2TBDMS,isomer #1CC(C)OCCOCC1=CC=C(OCC(CN(C(C)C)[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C)C=C12819.1Standard non polar33892256
Bisoprolol,2TBDMS,isomer #1CC(C)OCCOCC1=CC=C(OCC(CN(C(C)C)[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C)C=C12961.8Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Bisoprolol GC-MS (Non-derivatized) - 70eV, Positivesplash10-05g0-9851000000-9065ddf0b986c238395e2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Bisoprolol GC-MS (1 TMS) - 70eV, Positivesplash10-0006-9562000000-44cee6d913e8cf6bf7352017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Bisoprolol GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Bisoprolol GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Bisoprolol GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-11-05Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Bisoprolol GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-05Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Bisoprolol GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-11-05Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol LC-ESI-QFT , positive-QTOFsplash10-004i-0109000000-564ffde4ea3f59c4126f2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol LC-ESI-QFT , positive-QTOFsplash10-014i-2903000000-5e5b905ef2026aa7f0112017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol LC-ESI-QFT , positive-QTOFsplash10-00xr-9800000000-99ce6ca7b3171d63af092017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol LC-ESI-QFT , positive-QTOFsplash10-00di-9600000000-bfefc02f00a4439a34ba2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol LC-ESI-QFT , positive-QTOFsplash10-05fr-9500000000-4b91d206ced038eff35c2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol LC-ESI-QFT , positive-QTOFsplash10-0ab9-9400000000-dd6baeb57f900d719aa92017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol LC-ESI-QTOF , positive-QTOFsplash10-004i-0209000000-0f37dcfed3fc1c82c4702017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol LC-ESI-QTOF , positive-QTOFsplash10-014i-5902000000-dae2a435db6b3ea664cd2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol LC-ESI-QTOF , positive-QTOFsplash10-05fr-9200000000-1cce569461a677bb64672017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol , positive-QTOFsplash10-004i-0209000000-65dd49cd88f0ec1344452017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol LC-ESI-QFT , positive-QTOFsplash10-00or-5709000000-360e67ed724045a9c01b2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol 50V, Positive-QTOFsplash10-00ls-0900000000-9da1c89fab3eea35e2eb2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol 20V, Positive-QTOFsplash10-004i-0109000000-0803087ee41a5f4756c42021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol 10V, Positive-QTOFsplash10-004i-0009000000-4d3d24ad95cf8450432d2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol 30V, Positive-QTOFsplash10-014i-2903000000-a9ff8f842678e678f9102021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol 30V, Positive-QTOFsplash10-02vj-0902000000-601e7b32ea2f0c989a172021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol 40V, Positive-QTOFsplash10-001j-0900000000-215dd14dd5c87dd8442f2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol 15V, Positive-QTOFsplash10-004i-0109000000-0e51abd9a44743e421b72021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Bisoprolol 40V, Positive-QTOFsplash10-05fr-9200000000-1462679b0a1084c8ae262021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bisoprolol 10V, Positive-QTOFsplash10-00b9-4297000000-cc0bff99b7a745bbca622016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bisoprolol 20V, Positive-QTOFsplash10-00xr-7491000000-d270467937f89462ccd92016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bisoprolol 40V, Positive-QTOFsplash10-074l-9100000000-4cf48884e326a50699852016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bisoprolol 10V, Negative-QTOFsplash10-0ab9-5389000000-210c2d248c7ee6203c452016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bisoprolol 20V, Negative-QTOFsplash10-0a4i-7790000000-a567fd9f374a204b97ff2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Bisoprolol 40V, Negative-QTOFsplash10-0a4i-9400000000-6a382f7e8c32a2d8a71c2016-08-03Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00612 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00612 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00612
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2312
KEGG Compound IDC06852
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkBisoprolol
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID3127
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Horikiri Y, Suzuki T, Mizobe M: Pharmacokinetics and metabolism of bisoprolol enantiomers in humans. J Pharm Sci. 1998 Mar;87(3):289-94. [PubMed:9523980 ]
  2. Horikiri Y, Suzuki T, Mizobe M: Stereoselective metabolism of bisoprolol enantiomers in dogs and humans. Life Sci. 1998;63(13):1097-108. [PubMed:9763205 ]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Horikiri Y, Suzuki T, Mizobe M: Pharmacokinetics and metabolism of bisoprolol enantiomers in humans. J Pharm Sci. 1998 Mar;87(3):289-94. [PubMed:9523980 ]
  2. Horikiri Y, Suzuki T, Mizobe M: Stereoselective metabolism of bisoprolol enantiomers in dogs and humans. Life Sci. 1998;63(13):1097-108. [PubMed:9763205 ]
  3. Nozawa T, Taguchi M, Tahara K, Hashimoto Y, Igarashi N, Nonomura M, Kato B, Igawa A, Inoue H: Influence of CYP2D6 genotype on metoprolol plasma concentration and beta-adrenergic inhibition during long-term treatment: a comparison with bisoprolol. J Cardiovasc Pharmacol. 2005 Nov;46(5):713-20. [PubMed:16220080 ]
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular weight:
51322.1
References
  1. Breed JG, Ciampricotti R, Tromp GP, Valster FA, Lageweg E, Van Bortel LM: Quality of life perception during antihypertensive treatment: a comparative study of bisoprolol and enalapril. J Cardiovasc Pharmacol. 1992;20(5):750-5. [PubMed:1280737 ]
  2. Brouri F, Hanoun N, Mediani O, Saurini F, Hamon M, Vanhoutte PM, Lechat P: Blockade of beta 1- and desensitization of beta 2-adrenoceptors reduce isoprenaline-induced cardiac fibrosis. Eur J Pharmacol. 2004 Feb 6;485(1-3):227-34. [PubMed:14757145 ]
  3. Bruck H, Leineweber K, Temme T, Weber M, Heusch G, Philipp T, Brodde OE: The Arg389Gly beta1-adrenoceptor polymorphism and catecholamine effects on plasma-renin activity. J Am Coll Cardiol. 2005 Dec 6;46(11):2111-5. Epub 2005 Nov 4. [PubMed:16325050 ]
  4. Lipworth BJ, Irvine NA, McDevitt DG: A dose-ranging study to evaluate the beta 1-adrenoceptor selectivity of bisoprolol. Eur J Clin Pharmacol. 1991;40(2):135-9. [PubMed:1676675 ]
  5. Mauz AB, Pelzer H: Beta-adrenoceptor-binding studies of the cardioselective beta blockers bisoprolol, H-I 42 BS, and HX-CH 44 BS to heart membranes and intact ventricular myocytes of adult rats: two beta 1-binding sites for bisoprolol. J Cardiovasc Pharmacol. 1990 Mar;15(3):421-7. [PubMed:1691366 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine
Gene Name:
ADRB2
Uniprot ID:
P07550
Molecular weight:
46458.3
References
  1. Brouri F, Hanoun N, Mediani O, Saurini F, Hamon M, Vanhoutte PM, Lechat P: Blockade of beta 1- and desensitization of beta 2-adrenoceptors reduce isoprenaline-induced cardiac fibrosis. Eur J Pharmacol. 2004 Feb 6;485(1-3):227-34. [PubMed:14757145 ]
  2. Bruck H, Poller U, Lussenhop H, Ponicke K, Temme T, Heusch G, Philipp T, Brodde OE: Beta 2-adrenoceptor-mediated intrinsic sympathomimetic activity of carteolol: an in vivo study. Naunyn Schmiedebergs Arch Pharmacol. 2004 Nov;370(5):361-8. Epub 2004 Oct 23. [PubMed:15526107 ]
  3. Motomura S, Reinhard-Zerkowski H, Daul A, Brodde OE: On the physiologic role of beta-2 adrenoceptors in the human heart: in vitro and in vivo studies. Am Heart J. 1990 Mar;119(3 Pt 1):608-19. [PubMed:1968697 ]
  4. Brodde OE: Bisoprolol (EMD 33512), a highly selective beta 1-adrenoceptor antagonist: in vitro and in vivo studies. J Cardiovasc Pharmacol. 1986;8 Suppl 11:S29-35. [PubMed:2439795 ]
  5. Daul A, Johnston T, Reher M, Kruger M, Brodde OE: Differential haemodynamic effects induced by beta 1-(bisoprolol) or beta 2-(ICI 118,551) adrenoceptor blockade in man. J Hypertens Suppl. 1986 Dec;4(6):S99-102. [PubMed:2886573 ]