Details of the Drug

General Information of Drug (ID: DM3UZ95)

Drug Name

Bisoprolol

Synonyms

Bisocor; Bisoprololum; Cardicor; Concor; Detensiel; Emconcor; Emcor; Euradal; Isoten; Monocor; Soloc; Soprol; Zebeta; Bisoprolol fumerate; Bisoprolol hemifumarate; Bisoprololum [Latin]; CL-297939; Concor (TN); Concore (TN); EMD-33512; Monocor (TN); Zebeta (TN); Bisoprolol (USAN/INN); Bisoprolol [USAN:BAN:INN]; EMD-33-512; (+-)-1-((alpha-(2-Isopropoxyethoxy)-p-tolyl)oxy)-3-(isopropylamino)-2-propanol; (RS)-1-(4-(2-Isopropoxyethoxymethyl)phenoxy)-3-(isopropylamino)-2-propanol; 1-(propan-2-ylamino)-3-[4-(2-propan-2-yloxyethoxymethyl)phenoxy]propan-2-ol; 1-[(1-methylethyl)amino]-3-({4-[({2-[(1-methylethyl)oxy]ethyl}oxy)methyl]phenyl}oxy)propan-2-ol; 1-{4-[(2-isopropoxyethoxy)methyl]phenoxy}-3-(isopropylamino)propan-2-ol

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[1], [2]

Therapeutic Class

Antihypertensive Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

325.4

Topological Polar Surface Area (xlogp)

1.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2 h [3]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
Bioavailability: The bioavailability of drug is 95% [3]
Clearance: The total body clearance of drug is 14.2 L/h [5]
Elimination: About 50% of an oral dose is excreted unchanged in the urine with the remainder of the dose excreted as inactive bisoprolol metabolites [6]
Half-life: The concentration or amount of drug in body reduced by one-half in 10 - 12 hours (in healthy individuals) [7]
Metabolism: The drug is metabolized via the cytochrome P450 enzym CYP3A4 to inactive metabolites [6]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.877 micromolar/kg/day [8]
Unbound Fraction: The unbound fraction of drug in plasma is 0.66% [9]
Vd: The volume of distribution (Vd) of drug is 3.5 L/kg [10]

Chemical Identifiers

Formula: C18H31NO4
IUPAC Name: 1-(propan-2-ylamino)-3-[4-(2-propan-2-yloxyethoxymethyl)phenoxy]propan-2-ol
Canonical SMILES: CC(C)NCC(COC1=CC=C(C=C1)COCCOC(C)C)O
InChI: 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
InChIKey: VHYCDWMUTMEGQY-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 2405
ChEBI ID: CHEBI:3127
CAS Number: 66722-44-9
DrugBank ID: DB00612
TTD ID: D0K3ZR
INTEDE ID: DR0216
ACDINA ID: D00072

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Antagonist	[11], [12]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[13]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[14]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Bisoprolol

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Levamlodipine	DM92S6N	Moderate	Increased risk of cardiac depression by the combination of Bisoprolol and Levamlodipine.	Hypertension [BA00-BA04]	[40]
Verapamil	DMA7PEW	Major	Increased risk of cardiac depression by the combination of Bisoprolol and Verapamil.	Hypertension [BA00-BA04]	[40]
Indapamide	DMGN1PW	Moderate	Increased risk of hyperglycemia by the combination of Bisoprolol and Indapamide.	Hypertension [BA00-BA04]	[41]
Trichlormethiazide	DMHAQCO	Moderate	Increased risk of hypertriglyceridemia by the combination of Bisoprolol and Trichlormethiazide.	Hypertension [BA00-BA04]	[41]
Hydrochlorothiazide	DMUSZHD	Moderate	Increased risk of ventricular arrhythmias by the combination of Bisoprolol and Hydrochlorothiazide.	Hypertension [BA00-BA04]	[41]
Clevidipine butyrate	DMW4M97	Moderate	Increased risk of cardiac depression by the combination of Bisoprolol and Clevidipine butyrate.	Hypertension [BA00-BA04]	[40]
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⏷ Show the Full List of 6 DDI Information of This Drug

Coadministration of a Drug Treating the Disease Different from Bisoprolol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Scopolamine	DMOM8AL	Moderate	Antagonize the effect of Bisoprolol when combined with Scopolamine.	Addictive disorder [6C50-6C5Z]	[42]
Bepridil	DM0RKS4	Moderate	Increased risk of cardiac depression by the combination of Bisoprolol and Bepridil.	Angina pectoris [BA40]	[40]
Dronedarone	DMA8FS5	Moderate	Increased risk of atrioventricular block by the combination of Bisoprolol and Dronedarone.	Angina pectoris [BA40]	[43]
Nifedipine	DMSVOZT	Moderate	Increased risk of cardiac depression by the combination of Bisoprolol and Nifedipine.	Angina pectoris [BA40]	[40]
Zileuton	DMVRIC2	Moderate	Decreased metabolism of Bisoprolol caused by Zileuton.	Asthma [CA23]	[44]
Cariprazine	DMJYDVK	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Cariprazine.	Bipolar disorder [6A60]	[45]
Atracurium	DM42HXN	Moderate	Additive neuromuscular blocking effects by the combination of Bisoprolol and Atracurium.	Corneal disease [9A76-9A78]	[46]
Mivacurium	DM473VD	Moderate	Additive neuromuscular blocking effects by the combination of Bisoprolol and Mivacurium.	Corneal disease [9A76-9A78]	[46]
Tubocurarine	DMBZIVP	Moderate	Additive neuromuscular blocking effects by the combination of Bisoprolol and Tubocurarine.	Corneal disease [9A76-9A78]	[46]
Pasireotide	DMHM7JS	Moderate	Increased risk of bradycardia by the combination of Bisoprolol and Pasireotide.	Cushing syndrome [5A70]	[47]
OPC-34712	DMHG57U	Moderate	Additive hypotensive effects by the combination of Bisoprolol and OPC-34712.	Depression [6A70-6A7Z]	[45]
Mepenzolate	DM8YU2F	Moderate	Antagonize the effect of Bisoprolol when combined with Mepenzolate.	Digestive system disease [DE2Z]	[42]
Oxybutynine	DMJPBAX	Moderate	Antagonize the effect of Bisoprolol when combined with Oxybutynine.	Discovery agent [N.A.]	[42]
Ethacrynic acid	DM60QMR	Moderate	Increased risk of hyperglycemia by the combination of Bisoprolol and Ethacrynic acid.	Essential hypertension [BA00]	[41]
Phenoxybenzamine	DM8KSQH	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Phenoxybenzamine.	Essential hypertension [BA00]	[48]
Nicardipine	DMCDYW7	Moderate	Increased risk of cardiac depression by the combination of Bisoprolol and Nicardipine.	Essential hypertension [BA00]	[40]
Tolterodine	DMSHPW8	Moderate	Antagonize the effect of Bisoprolol when combined with Tolterodine.	Functional bladder disorder [GC50]	[42]
Propantheline	DM2EN6G	Moderate	Antagonize the effect of Bisoprolol when combined with Propantheline.	Gastric ulcer [DA60]	[42]
Chlorothiazide	DMLHESP	Moderate	Increased risk of hypertriglyceridemia by the combination of Bisoprolol and Chlorothiazide.	Heart failure [BD10-BD1Z]	[41]
Furosemide	DMMQ8ZG	Moderate	Increased risk of hyperglycemia by the combination of Bisoprolol and Furosemide.	Heart failure [BD10-BD1Z]	[41]
Bumetanide	DMRV7H0	Moderate	Increased risk of ventricular arrhythmias by the combination of Bisoprolol and Bumetanide.	Heart failure [BD10-BD1Z]	[41]
Hydroflumethiazide	DMVPUQI	Moderate	Increased risk of hyperglycemia by the combination of Bisoprolol and Hydroflumethiazide.	Heart failure [BD10-BD1Z]	[41]
Rifampin	DMA8J1G	Moderate	Increased metabolism of Bisoprolol caused by Rifampin mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[49]
Belladonna	DM2RBWK	Moderate	Antagonize the effect of Bisoprolol when combined with Belladonna.	Infectious gastroenteritis/colitis [1A40]	[42]
Propiomazine	DMKY8V1	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Propiomazine.	Insomnia [7A00-7A0Z]	[45]
ITI-007	DMUQ1DO	Moderate	Additive hypotensive effects by the combination of Bisoprolol and ITI-007.	Insomnia [7A00-7A0Z]	[45]
Clidinium	DMUMQZ0	Moderate	Antagonize the effect of Bisoprolol when combined with Clidinium.	Irritable bowel syndrome [DD91]	[42]
Dicyclomine	DMZSDGX	Moderate	Antagonize the effect of Bisoprolol when combined with Dicyclomine.	Irritable bowel syndrome [DD91]	[42]
Lanthanum carbonate	DMMJQSH	Moderate	Decreased absorption of Bisoprolol due to formation of complexes caused by Lanthanum carbonate.	Mineral absorption/transport disorder [5C64]	[47]
Thalidomide	DM70BU5	Moderate	Increased risk of ventricular arrhythmias by the combination of Bisoprolol and Thalidomide.	Multiple myeloma [2A83]	[50]
Siponimod	DM2R86O	Major	Increased risk of bradycardia by the combination of Bisoprolol and Siponimod.	Multiple sclerosis [8A40]	[50]
Fingolimod	DM5JVAN	Major	Increased risk of bradycardia by the combination of Bisoprolol and Fingolimod.	Multiple sclerosis [8A40]	[51]
Ozanimod	DMT6AM2	Moderate	Increased risk of atrioventricular block by the combination of Bisoprolol and Ozanimod.	Multiple sclerosis [8A40]	[52]
Promethazine	DM6I5GR	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Promethazine.	Nausea/vomiting [MD90]	[45]
Methylscopolamine	DM5VWOB	Moderate	Antagonize the effect of Bisoprolol when combined with Methylscopolamine.	Peptic ulcer [DA61]	[42]
Terazosin	DM3JCVS	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Terazosin.	Prostate hyperplasia [GA90]	[48]
Levomepromazine	DMIKFEL	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Levomepromazine.	Psychotic disorder [6A20-6A25]	[45]
Fluphenazine	DMIT8LX	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Fluphenazine.	Psychotic disorder [6A20-6A25]	[45]
Quetiapine	DM1N62C	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Quetiapine.	Schizophrenia [6A20]	[45]
Mesoridazine	DM2ZGAN	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Mesoridazine.	Schizophrenia [6A20]	[45]
Thioridazine	DM35M8J	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Thioridazine.	Schizophrenia [6A20]	[45]
Aripiprazole	DM3NUMH	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Aripiprazole.	Schizophrenia [6A20]	[45]
Iloperidone	DM6AUFY	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Iloperidone.	Schizophrenia [6A20]	[45]
Paliperidone	DM7NPJS	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Paliperidone.	Schizophrenia [6A20]	[45]
Perphenazine	DMA4MRX	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Perphenazine.	Schizophrenia [6A20]	[45]
Molindone	DMAH70G	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Molindone.	Schizophrenia [6A20]	[45]
Thiothixene	DMDINC4	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Thiothixene.	Schizophrenia [6A20]	[45]
Risperidone	DMN6DXL	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Risperidone.	Schizophrenia [6A20]	[45]
Amisulpride	DMSJVAM	Moderate	Increased risk of ventricular arrhythmias by the combination of Bisoprolol and Amisulpride.	Schizophrenia [6A20]	[42]
Asenapine	DMSQZE2	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Asenapine.	Schizophrenia [6A20]	[45]
Pipecuronium	DM5F84A	Moderate	Additive neuromuscular blocking effects by the combination of Bisoprolol and Pipecuronium.	Tonus and reflex abnormality [MB47]	[46]
Doxacurium	DMKE7L9	Moderate	Additive neuromuscular blocking effects by the combination of Bisoprolol and Doxacurium.	Tonus and reflex abnormality [MB47]	[46]
Vecuronium	DMP0UK2	Moderate	Additive neuromuscular blocking effects by the combination of Bisoprolol and Vecuronium.	Tonus and reflex abnormality [MB47]	[46]
Rocuronium	DMY9BMK	Moderate	Additive neuromuscular blocking effects by the combination of Bisoprolol and Rocuronium.	Tonus and reflex abnormality [MB47]	[46]
Methdilazine	DMAUHQX	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Methdilazine.	Vasomotor/allergic rhinitis [CA08]	[45]
Trimeprazine	DMEMV9D	Moderate	Additive hypotensive effects by the combination of Bisoprolol and Trimeprazine.	Vasomotor/allergic rhinitis [CA08]	[53]
Amiodarone	DMUTEX3	Moderate	Increased risk of atrioventricular block by the combination of Bisoprolol and Amiodarone.	Ventricular tachyarrhythmia [BC71]	[54]
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⏷ Show the Full List of 57 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Calcium hydrogenphosphate	E00294	24441	Diluent
Carmellose sodium	E00625	Not Available	Disintegrant
Crospovidone	E00626	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 6000	E00655	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
Certolake sunset yellow	E00351	61817	Colorant
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
Pregelatinized starch	E00674	Not Available	Binding agent; Diluent; Disintegrant
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⏷ Show the Full List of 25 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Bisoprolol 5 mg tablet	5 mg	Oral Tablet	Oral
Bisoprolol 10 mg tablet	10 mg	Oral Tablet	Oral
Bisoprolol Fumarate 5mg tablet	5mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7129).
2	Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4	BDDCS applied to over 900 drugs
5	Kirch W, Rose I, Demers HG, Leopold G, Pabst J, Ohnhaus EE: Pharmacokinetics of bisoprolol during repeated oral administration to healthy volunteers and patients with kidney or liver disease. Clin Pharmacokinet. 1987 Aug;13(2):110-7. doi: 10.2165/00003088-198713020-00003.
6	Bisoprolol monograph
7	Pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist. Br J Clin Pharmacol. 1986 Sep;22(3):293-300. doi: 10.1111/j.1365-2125.1986.tb02890.x.
8	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
9	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
10	Summary of product characteristics
11	Antiarrhythmic effect of bisoprolol, a highly selective beta1-blocker, in patients with paroxysmal atrial fibrillation. Int Heart J. 2008 May;49(3):281-93.
12	Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the beta 1-adrenoceptor with positive chronotropic effect. Circulation. 1994 Jun;89(6):2760-7.
13	Stereoselective metabolism of bisoprolol enantiomers in dogs and humans. Life Sci. 1998;63(13):1097-108.
14	Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22.
15	Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
16	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
17	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
18	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
19	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
20	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
21	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
22	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
23	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
24	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
25	Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
26	CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
27	Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
28	Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
29	Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
30	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
31	Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
32	Beta-blockers in the treatment of hypertension: are there clinically relevant differences Postgrad Med. 2009 May;121(3):90-8.
33	Adrenergic activation of electrogenic K+ secretion in guinea pig distal colonic epithelium: involvement of beta1- and beta2-adrenergic receptors. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G269-77.
34	Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med. 1999 Feb;27(2):325-31.
35	Prediction and experimental validation of acute toxicity of beta-blockers in Ceriodaphnia dubia. Environ Toxicol Chem. 2005 Oct;24(10):2470-6.
36	Topical dorzolamide 2%/timolol 0.5% ophthalmic solution: a review of its use in the treatment of glaucoma and ocular hypertension. Drugs Aging. 2006;23(12):977-95.
37	Current therapeutic uses and potential of beta-adrenoceptor agonists and antagonists. Eur J Clin Pharmacol. 1998 Feb;53(6):389-404.
38	beta-adrenergic enhancement of brain kynurenic acid production mediated via cAMP-related protein kinase A signaling. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Apr 30;33(3):519-29.
39	beta(2)-adrenoceptors are critical for antidepressant treatment of neuropathic pain. Ann Neurol. 2009 Feb;65(2):218-25.
40	Anastassiades CJ "Nifedipine and beta-blocker drugs." Br Med J 281 (1980): 1251-2. [PMID: 6107167]
41	Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA "Nadolol in combination with indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol 28 (1985): 29-33. [PMID: 3987783]
42	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
43	Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
44	Product Information. Zylo Filmtab (zileuton). Abbott Pharmaceutical, Abbott Park, IL.
45	Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
46	Chapple DJ, Clark JS, Hughes R "Interaction between atracurium and drugs used in anaesthesia." Br J Anaesth 55 Suppl 1 (1983): s17-22. [PMID: 6688011]
47	Canadian Pharmacists Association.
48	Chrysant SG "Experience with terazosin administered in combination with other antihypertensive agents." Am J Med 80 (1986): 55-61. [PMID: 2872808]
49	Kirch W, Rose I, Klingmann I, Pabst J, Ohnhaus EE "Interaction of bisoprolol with cimetidine and rifampicin." Eur J Clin Pharmacol 31 (1986): 59-62. [PMID: 2877885]
50	Cerner Multum, Inc. "Australian Product Information.".
51	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
52	Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
53	Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
54	Leor J, Levartowsky D, Sharon C, Farfel Z "Amiodarone and beta-adrenergic blockers: an interaction with metoprolol but not with atenolol." Am Heart J 16 (1988): 206-7. [PMID: 3394625]