Identification

Name
Timolol
Accession Number
DB00373  (APRD00229, DB08625)
Type
Small Molecule
Groups
Approved
Description

A beta-adrenergic antagonist similar in action to propranolol. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of migraine disorders and tremor. [PubChem]

Structure
Thumb
Synonyms
  • (S)-1-(tert-butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol
  • Timolol
  • Timolol anhydrous
  • Timololo
  • Timololum
External IDs
MK 950
Product Ingredients
IngredientUNIICASInChI Key
Timolol hemihydrate817W3C617591524-16-2TWBNMYSKRDRHAT-RCWTXCDDSA-N
Timolol maleateP8Y54F701R26921-17-5WLRMANUAADYWEA-NWASOUNVSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Beta-tim - 0.25% LiqLiquid0.25 %OphthalmicCiba Vision1994-12-311998-07-16Canada
Beta-tim - 0.5% LiqLiquid0.5 %OphthalmicCiba Vision1994-12-311998-07-16Canada
BetimolSolution / drops5.12 mg/1mLOphthalmicOak Pharmaceuticals, Inc. (Subsidiary of Akorn, Inc.) (968937719)2014-01-02Not applicableUs
BetimolSolution5 mg/1mLOphthalmicVistakon Pharmaceuticals2000-10-01Not applicableUs
BetimolSolution / drops2.56 mg/1mLOphthalmicOak Pharmaceuticals, Inc. (Subsidiary of Akorn, Inc.) (968937719)2014-01-02Not applicableUs
BetimolSolution2.5 mg/1mLOphthalmicVistakon Pharmaceuticals2000-10-01Not applicableUs
BlocadrenTablet20 mg/1OralMerck Sharp & Dohme Limited1981-11-252004-08-31Us
BlocadrenTablet10 mg/1OralMerck Sharp & Dohme Limited1981-11-252004-08-31Us
BlocadrenTablet5 mg/1OralMerck Sharp & Dohme Limited1981-11-252004-08-31Us
Blocadren Tab 10mgTablet10 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1977-12-312000-08-03Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-timopSolution0.5 %OphthalmicApotex Corporation1988-12-31Not applicableCanada
Apo-timopSolution0.25 %OphthalmicApotex Corporation1988-12-31Not applicableCanada
Apo-timop GelSolution, gel forming, extended release0.25 %OphthalmicApotex CorporationNot applicableNot applicableCanada
Apo-timop GelSolution, gel forming, extended release0.5 %OphthalmicApotex Corporation2008-02-20Not applicableCanada
Dom-timololSolution0.5 %OphthalmicDominion Pharmacal1999-03-08Not applicableCanada
Dom-timololSolution0.25 %OphthalmicDominion Pharmacal1999-03-08Not applicableCanada
Jamp-timololSolution0.5 %OphthalmicJamp Pharma Corporation2015-11-20Not applicableCanada
Mylan-timololSolution0.5 %OphthalmicMylan Pharmaceuticals1992-12-312012-10-19Canada
Mylan-timololSolution0.25 %OphthalmicMylan Pharmaceuticals1992-12-312012-10-19Canada
Novo-timol Liq 0.25%Liquid0.25 %OphthalmicNovopharm Limited1993-12-312015-10-26Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Act DorzotimololTimolol (5 mg) + Dorzolamide (20 mg)SolutionOphthalmicTeva2013-05-01Not applicableCanada
Act Latanoprost/timololTimolol (5 mg) + Latanoprost (50 mcg)SolutionOphthalmicActavis Pharma Company2015-09-29Not applicableCanada
Apo-dorzo-timopTimolol (5 mg) + Dorzolamide (20 mg)SolutionOphthalmicApotex Corporation2010-12-15Not applicableCanada
Apo-latanoprost-timopTimolol (5 mg) + Latanoprost (50 mcg)SolutionOphthalmicApotex Corporation2014-07-02Not applicableCanada
Apo-travoprost-timopTimolol (0.5 %) + Travoprost (0.004 %)SolutionOphthalmicApotex CorporationNot applicableNot applicableCanada
AzargaTimolol (0.5 %) + Brinzolamide (1 %)SuspensionOphthalmicNovartis2009-08-25Not applicableCanada
AzargaTimolol maleate (5 mg/ml) + Brinzolamide (10 mg/ml)Suspension / dropsOphthalmicNovartis Europharm Limited2008-11-25Not applicableEu
AzargaTimolol maleate (5 mg/ml) + Brinzolamide (10 mg/ml)Suspension / dropsOphthalmicNovartis Europharm Limited2008-11-25Not applicableEu
CombiganTimolol maleate (5 mg/1mL) + Brimonidine tartrate (2 mg/1mL)Solution / dropsOphthalmicPhysicians Total Care, Inc.2011-08-29Not applicableUs
CombiganTimolol maleate (5 mg/1mL) + Brimonidine tartrate (2 mg/1mL)Solution / dropsOphthalmicAllergan2007-11-14Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Tim-Brim-Dor PFTimolol maleate (5 mg/1mL) + Brimonidine tartrate (1.5 mg/1mL) + Dorzolamide Hydrochloride (20 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Tim-Brim-Dor-LatTimolol maleate (5 mg/1mL) + Brimonidine tartrate (1.5 mg/1mL) + Dorzolamide Hydrochloride (20 mg/1mL) + Latanoprost (0.05 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Tim-Dor PFTimolol maleate (5 mg/1mL) + Dorzolamide Hydrochloride (20 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Tim-Dor-LatTimolol maleate (5 mg/1mL) + Dorzolamide Hydrochloride (20 mg/1mL) + Latanoprost (0.05 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Tim-Lat -PFTimolol maleate (5 mg/1mL) + Latanoprost (0.05 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
International/Other Brands
Blocadren (Merck) / Proflax (Sidus) / Tenopt (Sigma) / Timacar Depot (MSD) / Timacor (Gerda) / Timoptol (Merck)
Categories
UNII
5JKY92S7BR
CAS number
26839-75-8
Weight
Average: 316.42
Monoisotopic: 316.156911344
Chemical Formula
C13H24N4O3S
InChI Key
BLJRIMJGRPQVNF-JTQLQIEISA-N
InChI
InChI=1S/C13H24N4O3S/c1-13(2,3)14-8-10(18)9-20-12-11(15-21-16-12)17-4-6-19-7-5-17/h10,14,18H,4-9H2,1-3H3/t10-/m0/s1
IUPAC Name
(2S)-1-(tert-butylamino)-3-{[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy}propan-2-ol
SMILES
[H][C@](O)(CNC(C)(C)C)COC1=NSN=C1N1CCOCC1

Pharmacology

Indication

In its oral form it is used to treat high blood pressure and prevent heart attacks, and occasionally to prevent migraine headaches. In its opthalmic form it is used to treat open-angle and occasionally secondary glaucoma.

Associated Conditions
Pharmacodynamics

Similar to propranolol and nadolol, timolol is a non-selective, beta-adrenergic receptor antagonist. Timolol does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity, but does possess a relatively high degree of lipid solubility. Timolol, when applied topically to the eye, has the action of reducing elevated, as well as normal, intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss and optic nerve damage.

Mechanism of action

Like propranolol and nadolol, timolol competes with adrenergic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart and vascular smooth muscle and beta(2)-receptors in the bronchial and vascular smooth muscle. Beta(1)-receptor blockade results in a decrease in resting and exercise heart rate and cardiac output, a decrease in both systolic and diastolic blood pressure, and, possibly, a reduction in reflex orthostatic hypotension. Beta(2)-blockade results in an increase in peripheral vascular resistance. The exact mechanism whereby timolol reduces ocular pressure is still not known. The most likely action is by decreasing the secretion of aqueous humor.

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Human
ABeta-2 adrenergic receptor
antagonist
Human
ULysozymeNot AvailableEnterobacteria phage T4
Absorption

Bioavailability is about 60%

Volume of distribution
Not Available
Protein binding

~10%

Metabolism

Primarily hepatic (80%) via the cytochrome P450 2D6 isoenzyme.

Route of elimination

Timolol and its metabolites are primarily excreted in the urine.

Half life

2.5-5 hours

Clearance
Not Available
Toxicity

LD50=1190 mg/kg (oral, mice), LD50=900 mg/kg (oral, rat). Symptoms of overdose include drowsiness, vertigo, headache, and atriventricular block.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Timolol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details

Interactions

Drug Interactions
DrugInteraction
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Timolol.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Timolol is combined with 3-isobutyl-1-methyl-7H-xanthine.
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Timolol.
6-O-benzylguanineThe risk or severity of adverse effects can be increased when Timolol is combined with 6-O-benzylguanine.
7-DeazaguanineThe risk or severity of adverse effects can be increased when Timolol is combined with 7-Deazaguanine.
7,9-DimethylguanineThe risk or severity of adverse effects can be increased when Timolol is combined with 7,9-Dimethylguanine.
8-azaguanineThe risk or severity of adverse effects can be increased when Timolol is combined with 8-azaguanine.
8-chlorotheophyllineThe risk or severity of adverse effects can be increased when Timolol is combined with 8-chlorotheophylline.
9-DeazaguanineThe risk or severity of adverse effects can be increased when Timolol is combined with 9-Deazaguanine.
9-MethylguanineThe risk or severity of adverse effects can be increased when Timolol is combined with 9-Methylguanine.
Food Interactions
Not Available

References

Synthesis Reference

Markku Per alampi, "S-timolol hemihydrate composition and method of preparation therefor." U.S. Patent US5574035, issued October, 1986.

US5574035
General References
  1. Link [Link]
External Links
KEGG Compound
C07141
PubChem Compound
33624
PubChem Substance
46507733
ChemSpider
31013
BindingDB
50292219
ChEBI
9599
ChEMBL
CHEMBL499
Therapeutic Targets Database
DAP000088
PharmGKB
PA451690
HET
TIM
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Timolol
ATC Codes
C07DA06 — Timolol, thiazides and other diureticsS01ED01 — TimololS01ED51 — Timolol, combinationsC07AA06 — TimololC07BA06 — Timolol and thiazides
AHFS Codes
  • 52:40.08 — Beta-adrenergic Agents
  • 24:24.00 — Beta-adrenergic Blocking Agents
  • 52:92.00 — EENT Drugs, Miscellaneous
PDB Entries
3d4s
FDA label
Download (471 KB)
MSDS
Download (73.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedOtherGlaucoma / Ophthalmic Solutions1
0Unknown StatusTreatmentHemangiomas / Infants1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentEye Diseases / Glaucoma / Ocular Hypertension1
1CompletedTreatmentGlaucoma1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)1
1RecruitingTreatmentAcne Vulgaris / Rosaceas1
1RecruitingTreatmentGlaucoma1
1RecruitingTreatmentPort-wine Mark / Sturge Weber Syndrome1
1TerminatedPreventionInfantile Hemangiomas / Very Low Birth Weight Infants1
1WithdrawnTreatmentAnterior Ischemic Optic Neuropathy / Ischemic Optic Neuropathy / Optic Neuropathy, Anterior Ischemic / Optic Neuropathy, Ischemic1
1, 2CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)3
1, 2Unknown StatusTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
2Active Not RecruitingTreatmentGlaucoma Open-Angle1
2Active Not RecruitingTreatmentGlaucoma and Ocular Hypertension1
2CompletedPreventionEsophageal and Gastric Varices / Liver Cirrhosis / Portal Hypertension1
2CompletedTreatmentAge-Related Macular Degeneration (ARMD) / Diabetic Macular Edema (DME) / Retinal Vein Occlusions(RVO) / Wet Macular Degeneration1
2CompletedTreatmentGlaucoma2
2CompletedTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension4
2CompletedTreatmentGlaucoma / Ocular Hypertension2
2CompletedTreatmentHemangiomas1
2CompletedTreatmentHemorrhagic Hereditary Telangiectasia (HHT)1
2CompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)2
2CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)3
2CompletedTreatmentOpen Angle Glaucoma (OAG)1
2CompletedTreatmentVenous Leg Ulcer (VLU)1
2Not Yet RecruitingNot AvailableHealthy Volunteers1
2RecruitingTreatmentHemangiomas1
2TerminatedTreatmentGlaucoma1
2TerminatedTreatmentMinor burns / Ulcers1
2Unknown StatusTreatmentHypertensive Phase1
2WithdrawnTreatmentInfantile Hemangiomas1
2, 3CompletedBasic ScienceOpen-angle Glaucoma (OAG)1
2, 3RecruitingTreatmentNeovascular Age-Related Macular Degeneration / Wet Macular Degeneration1
3Active Not RecruitingTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)2
3CompletedPreventionEsophageal and Gastric Varices / Liver Cirrhosis / Portal Hypertension1
3CompletedTreatmentGlaucoma3
3CompletedTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension4
3CompletedTreatmentGlaucoma / Ocular Hypertension8
3CompletedTreatmentGlaucoma / Ocular Hypertension / Open Angle Glaucoma (OAG)1
3CompletedTreatmentGlaucoma / Ocular Hypertension / Open-angle Glaucoma (OAG)1
3CompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)6
3CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)18
3CompletedTreatmentOpen Angle Glaucoma or Ocular Hypertension1
3Not Yet RecruitingTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
3RecruitingPreventionGlaucoma1
3RecruitingTreatmentChronic Diabetic Foot Ulcers / Diabetic Neuropathic Ulcers / Non Healing Wound1
3RecruitingTreatmentGlaucoma, Primary Open Angle (POAG)1
3TerminatedBasic ScienceHealthy Volunteers1
3TerminatedTreatmentGlaucoma1
3TerminatedTreatmentGlaucoma / Ocular Hypertension1
3TerminatedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)1
3Unknown StatusTreatmentCorneal Edema / Visual Acuity1
3Unknown StatusTreatmentGlaucoma2
3Unknown StatusTreatmentMelanoma1
3WithdrawnPreventionHemorrhage, Gastrointestinal / Portal Hypertension1
4Active Not RecruitingDiagnosticGlaucoma, Primary Open Angle (POAG) / Glaucoma; Drugs / Normal Tension Glaucoma1
4CompletedNot AvailableOcular Hypertension / Open-angle Glaucoma (OAG)1
4CompletedNot AvailableOpen-angle Glaucoma (OAG)1
4CompletedBasic ScienceGlaucoma1
4CompletedOtherEye Disease1
4CompletedTreatmentAnterior Uveitis (AU) / Cystoid Macular Edema1
4CompletedTreatmentExfoliation Syndrome / Ocular Hypertension / Open-angle Glaucoma (OAG) / Pigmentary Glaucoma1
4CompletedTreatmentEye Diseases / Glaucoma / Open-angle Glaucoma (OAG)1
4CompletedTreatmentGlaucoma12
4CompletedTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
4CompletedTreatmentGlaucoma / Ocular Hypertension9
4CompletedTreatmentGlaucoma / Ocular Hypertension / Open-angle Glaucoma (OAG)1
4CompletedTreatmentGlaucoma / Ocular Surface Disease1
4CompletedTreatmentOcular Hypertension1
4CompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)3
4CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)8
4CompletedTreatmentOpen Angle Glaucoma (OAG)1
4CompletedTreatmentOpen-angle Glaucoma (OAG)1
4RecruitingTreatmentGlaucoma1
4TerminatedTreatmentGlaucoma1
4TerminatedTreatmentGlaucoma, Angle-Closure1
4TerminatedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)1
4Unknown StatusBasic ScienceOpen Angle Glaucoma (OAG)1
4Unknown StatusTreatmentGlaucoma1
4Unknown StatusTreatmentNormal Tension Glaucoma1
4WithdrawnPreventionGlaucoma / Ocular Hypertension / Thyroid Eye Disease1
4WithdrawnTreatmentBenign Vascular Periocular Lesions1
Not AvailableCompletedNot AvailableGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
Not AvailableCompletedNot AvailableGlaucoma / Ocular Hypertension2
Not AvailableCompletedNot AvailableOcular Hypertension / Open-angle Glaucoma (OAG)4
Not AvailableCompletedBasic ScienceDrug Effect (Glaucoma Drugs)1
Not AvailableCompletedBasic ScienceGlaucoma1
Not AvailableCompletedPreventionIntraocular Pressure Change in Intravitreal Injection1
Not AvailableCompletedTreatmentGlaucoma / Ocular Hypertension1
Not AvailableCompletedTreatmentMacular Hole / Retinal Detachment1
Not AvailableCompletedTreatmentMyopic Regression1
Not AvailableCompletedTreatmentNormal Tension Glaucoma1
Not AvailableCompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)1
Not AvailableCompletedTreatmentPhysiology, Ocular / Retina1
Not AvailableNot Yet RecruitingPreventionOcular Hypertension1
Not AvailableRecruitingNot AvailableAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB) / Acute Bacterial Sinusitis (ABS) / Acute Decompensated Heart Failure (ADHF) / Acute Pyelonephritis / Adenovirus / Adjunct to general anesthesia therapy / Adrenal Insufficiency / Airway Swelling / Anaesthesia therapy / Anxiolysis / Arterial Hypotension / Autism, Early Infantile / Autistic Disorder / Bartonellosis / Benzodiazepine Withdrawal / Benzodiazepines / Bipolar Disorder (BD) / Bloodstream Infections / Bone and Joint Infections / Brain Swelling / Bronchospasm / Brucellosis / Cardiac Arrest / Central Nervous System Infections / Cholera / Chronic Bacterial Prostatitis / Community Acquired Pneumonia (CAP) / Complicated Urinary Tract Infections / Convulsions / Cyanide Poisoning / Cytomegalovirus Retinitis / Drug hypersensitivity reaction / Early-onset Schizophrenia Spectrum Disorders / Edema / Epilepsies / Feeling Anxious / Flu caused by Influenza / Gastroparesis / Gynaecological infection / Headaches / Herpes Simplex Virus / High Blood Cholesterol Level / High Blood Pressure (Hypertension) / Hospital-acquired bacterial pneumonia / Hyperlipidemias / Infantile Hemangiomas / Infection NOS / Inflammatory Conditions / Inflammatory Reaction / Influenza Treatment or Prophylaxis / Inhalational Anthrax (Post-Exposure) / Intra-Abdominal Infections / Life-threatening Fungal Infections / Lower Respiratory Tract Infection (LRTI) / Meningitis, Bacterial / Migraines / Muscle Spasms / Nausea / Opioid Addiction / Pain / Plague / Pneumonia / Prophylaxis / Psittacosis / Q Fever / Reflux / Relapsing Fever / Rocky Mountain Spotted Fever / Schizophrenic Disorders / Sedation therapy / Seizures / Sepsis / Skeletal Muscle Spasms / Skin and Subcutaneous Tissue Bacterial Infections / Skin Structures and Soft Tissue Infections / Stable Angina (SA) / Thromboprophylaxis / Thrombosis / Trachoma / Treatment-resistant Schizophrenia / Tularemia / Typhus Fever / Uncomplicated Skin and Skin Structure Infections / Uncomplicated Urinary Tract Infections / Urinary Tract Infections (UTIs) / Vomiting / Withdrawal1
Not AvailableRecruitingPreventionHemangiomas1
Not AvailableRecruitingTreatmentComplications of Diabetes Mellitus1
Not AvailableRecruitingTreatmentHereditary Haemorrhagic Telangiectasia (HHT)1
Not AvailableUnknown StatusHealth Services ResearchOpen Angle Glaucoma (OAG)1
Not AvailableUnknown StatusTreatmentExfoliation Syndrome / Glaucoma / Ocular Hypertension1
Not AvailableWithdrawnNot AvailableOcular Hypertension / Open-angle Glaucoma (OAG)1
Not AvailableWithdrawnBasic ScienceGlaucoma1

Pharmacoeconomics

Manufacturers
  • Santen oy
  • Falcon pharmaceuticals ltd
  • Aton pharma inc
  • Ista pharmaceuticals
  • Akorn inc
  • Bausch and lomb pharmaceuticals inc
  • Bausch and lomb inc
  • Falcon pharmaceuticals inc
  • Fdc ltd
  • E fougera div altana inc
  • Hi tech pharmacal co inc
  • Novex pharma
  • Pacific pharma inc
  • Pacific pharma
  • Wockhardt ltd
  • Merck research laboratories div merck co inc
  • Mylan pharmaceuticals inc
  • Quantum pharmics ltd
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Usl pharma inc
  • Watson laboratories inc
Packagers
  • Akorn Inc.
  • Alcon Laboratories
  • Allergan Inc.
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Aton Pharma Inc.
  • Bausch & Lomb Inc.
  • Dispensing Solutions
  • E. Fougera and Co.
  • Endo Pharmaceuticals Inc.
  • Falcon Pharmaceuticals Ltd.
  • Hi Tech Pharmacal Co. Inc.
  • ISTA Pharmaceuticals
  • Major Pharmaceuticals
  • Medisca Inc.
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novex Pharma
  • Novopharm Ltd.
  • Pacific Pharma Lp
  • Pack Pharmaceuticals
  • Palmetto Pharmaceuticals Inc.
  • PCAS Finland Oy
  • Person & Covey
  • Pharmedix
  • Physicians Total Care Inc.
  • Prasco Labs
  • Qualitest
  • Sandhills Packaging Inc.
  • Sandoz
  • Santen Inc.
  • Vistakon Pharmaceuticals LLC
Dosage forms
FormRouteStrength
SuspensionOphthalmic
Suspension / dropsOphthalmic
LiquidOphthalmic0.25 %
LiquidOphthalmic0.5 %
SolutionOphthalmic2.5 mg/1mL
SolutionOphthalmic5 mg/1mL
Solution / dropsOphthalmic2.56 mg/1mL
Solution / dropsOphthalmic5.12 mg/1mL
TabletOral10 mg/1
TabletOral20 mg/1
TabletOral5 mg/1
Solution / dropsOphthalmic
SolutionOphthalmic0.25 %
SolutionOphthalmic0.5 %
TabletOral10 mg
TabletOral20 mg
TabletOral5 mg
TabletOral
SolutionOphthalmic6.8 mg/1mL
Solution / dropsOphthalmic2.5 mg/1mL
Solution / dropsOphthalmic5 mg/1mL
Solution / dropsOphthalmic5.0 mg/1mL
Solution / dropsOphthalmic6.8 mg/1mL
SolutionOphthalmic.25 %
SolutionOphthalmic3.4 mg/1mL
SolutionOphthalmic5.0 mg/1mL
Solution, gel forming, extended releaseOphthalmic0.25 %
Solution, gel forming, extended releaseOphthalmic0.5 %
Solution, gel forming, extended releaseOphthalmic2.5 mg/1mL
Solution, gel forming, extended releaseOphthalmic5 mg/1mL
SolutionOphthalmic
Prices
Unit descriptionCostUnit
Betimol 0.5% Solution 15ml Bottle152.24USD bottle
Timolol maleate powder107.1USD g
Betimol 0.5% Solution 10ml Bottle106.88USD bottle
Betimol 0.25% Solution 15ml Bottle93.56USD bottle
Timoptic-XE 0.5% Gel Forming Solution 5ml Bottle85.09USD bottle
Timoptic 0.5% Solution 10ml Bottle83.2USD bottle
Timoptic-XE 0.25% Gel Forming Solution 5ml Bottle65.37USD bottle
Betimol 0.5% Solution 5ml Bottle63.43USD bottle
Timolol Maleate 0.5% Gel Forming Solution 5ml Bottle60.84USD bottle
Timoptic 0.5% Solution 5ml Bottle59.8USD bottle
Timolol Maleate 0.25% Gel Forming Solution 5ml Bottle59.71USD bottle
Betimol 0.25% Solution 5ml Bottle55.56USD bottle
Timolol Maleate 0.5% Solution 15ml Bottle50.7USD bottle
Betimol 0.25% Solution 10ml Bottle49.99USD bottle
Timolol Maleate 0.5% Gel Forming Solution 2.5ml Bottle46.74USD bottle
Timolol Maleate 0.25% Solution 15ml Bottle43.68USD bottle
Timoptic 0.25% Solution 5ml Bottle43.06USD bottle
Istalol 0.5% eye drops36.43USD ml
Timolol Maleate 0.5% Solution 10ml Bottle33.58USD bottle
Timolol Maleate 0.25% Solution 10ml Bottle28.87USD bottle
Timoptic-XE 0.25% Gel Forming Solution 2.5ml Bottle23.99USD bottle
Timolol Maleate 0.5% Solution 5ml Bottle17.68USD bottle
Timolol Maleate 0.25% Solution 5ml Bottle15.6USD bottle
Timoptic-xe 0.5% eye solution13.6USD ml
Timoptic-xe 0.25% eye solution11.51USD ml
Betimol 0.5% eye drops10.15USD ml
Betimol 0.25% eye drops9.19USD ml
Timoptic 0.5% eye drops8.63USD ml
Timoptic 0.25% eye drops7.32USD ml
Timoptic-Xe 0.5 % Long Acting Gellan Solution4.64USD ml
Timoptic 0.5% ocudose drops4.57USD each
Timoptic-Xe 0.25 % Long Acting Gellan Solution3.88USD ml
Timoptic 0.25% ocudose drops3.8USD each
Timoptic 0.5 % Solution3.63USD ml
Timolol 0.5% eye drops3.24USD ml
Timolol 0.25% eye drops2.78USD ml
Apo-Timop 0.5 % Solution1.95USD ml
Mylan-Timolol 0.5 % Solution1.95USD ml
Pms-Timolol 0.5 % Solution1.95USD ml
Sandoz Timolol Maleate 0.5 % Solution1.95USD ml
Apo-Timop 0.25 % Solution1.62USD ml
Mylan-Timolol 0.25 % Solution1.62USD ml
Pms-Timolol 0.25 % Solution1.62USD ml
Sandoz Timolol Maleate 0.25 % Solution1.62USD ml
Timolol maleate 20 mg tablet0.94USD tablet
Hydrocortisone 2.5% lotion0.6USD ml
Apo-Timol 20 mg Tablet0.59USD tablet
Novo-Timol 20 mg Tablet0.59USD tablet
Timolol maleate 10 mg tablet0.51USD tablet
Timolol maleate 5 mg tablet0.41USD tablet
Apo-Timol 10 mg Tablet0.3USD tablet
Novo-Timol 10 mg Tablet0.3USD tablet
Nu-Timolol 10 mg Tablet0.3USD tablet
Apo-Timol 5 mg Tablet0.19USD tablet
Novo-Timol 5 mg Tablet0.19USD tablet
Nu-Timolol 5 mg Tablet0.19USD tablet
Aquanil hc 1% lotion0.12USD ml
Aquanil cleanser0.03USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5231095No1993-07-272010-07-27Us
US6174524Yes1999-09-262019-09-26Us
US7030149No2002-04-192022-04-19Us
US7320976No2002-04-192022-04-19Us
US7642258No2002-04-192022-04-19Us
US8133890No2002-04-192022-04-19Us
US8354409No2002-04-192022-04-19Us
US8748425No2002-04-192022-04-19Us
US7323463No2003-01-192023-01-19Us
US6335335No1998-11-022018-11-02Us
US6645963No1998-11-162018-11-16Us
US9474751No2002-04-192022-04-19Us
US9770453No2002-04-192022-04-19Us
US9907801No2002-04-192022-04-19Us
US9907802No2002-04-192022-04-19Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)202 °CPhysProp
water solubility2.74 mg/mLNot Available
logP1.83HANSCH,C ET AL. (1995)
Caco2 permeability-4.85ADME Research, USCD
pKa9.21KONTTURI,K & MURTOMAKI,L (1992)
Predicted Properties
PropertyValueSource
Water Solubility0.269 mg/mLALOGPS
logP1.44ALOGPS
logP1.34ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)14.08ChemAxon
pKa (Strongest Basic)9.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area79.74 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity83.92 m3·mol-1ChemAxon
Polarizability33.86 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9958
Blood Brain Barrier-0.6467
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.8522
P-glycoprotein inhibitor INon-inhibitor0.6567
P-glycoprotein inhibitor IINon-inhibitor0.9552
Renal organic cation transporterNon-inhibitor0.9105
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.5389
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8678
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.7338
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6096 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9214
hERG inhibition (predictor II)Non-inhibitor0.7334
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-0009000000-d71d621ed511e13fd0fc
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-02t9-0069000000-b1978af1db9940bfb5e5
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-01vx-4390000000-df83be04a7e7c18de424
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-9410000000-c9b47edd2cfab49a0aef
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-9300000000-617e94c43fe73fa575e6
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-03di-0090000000-da0c1e25ae5110879b00
MS/MS Spectrum - , positiveLC-MS/MSsplash10-02t9-0379000000-8b822b96645d698d2c82

Taxonomy

Description
This compound belongs to the class of organic compounds known as dialkylarylamines. These are aliphatic aromatic amines in which the amino group is linked to two aliphatic chains and one aromatic group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Dialkylarylamines
Alternative Parents
Alkyl aryl ethers / Morpholines / Imidolactams / Thiadiazoles / Heteroaromatic compounds / Secondary alcohols / 1,2-aminoalcohols / Oxacyclic compounds / Dialkylamines / Dialkyl ethers
show 3 more
Substituents
Dialkylarylamine / Alkyl aryl ether / Morpholine / Oxazinane / Imidolactam / Azole / Heteroaromatic compound / Thiadiazole / 1,2-aminoalcohol / Secondary alcohol
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
timolol (CHEBI:9599)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor signaling protein activity
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 e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Nieminen T, Uusitalo H, Maenpaa J, Turjanmaa V, Rane A, Lundgren S, Ropo A, Rontu R, Lehtimaki T, Kahonen M: Polymorphisms of genes CYP2D6, ADRB1 and GNAS1 in pharmacokinetics and systemic effects of ophthalmic timolol. A pilot study. Eur J Clin Pharmacol. 2005 Dec;61(11):811-9. Epub 2005 Nov 17. [PubMed:16315032]
  3. Varma DR, Shen H, Deng XF, Peri KG, Chemtob S, Mulay S: Inverse agonist activities of beta-adrenoceptor antagonists in rat myocardium. Br J Pharmacol. 1999 Jun;127(4):895-902. [PubMed:10433496]
  4. Hirooka K, Kelly ME, Baldridge WH, Barnes S: Suppressive actions of betaxolol on ionic currents in retinal ganglion cells may explain its neuroprotective effects. Exp Eye Res. 2000 May;70(5):611-21. [PubMed:10870519]
  5. Bhattacharyya BJ, Lee E, Krupin D, Hockberger P, Krupin T: (-)-Isoproterenol modulation of maxi-K(+) channel in nonpigmented ciliary epithelial cells through a G-protein gated pathway. Curr Eye Res. 2002 Mar;24(3):173-81. [PubMed:12221524]
  6. Wang T, Kaumann AJ, Brown MJ: (--)-Timolol is a more potent antagonist of the positive inotropic effects of (--)-adrenaline than of those of (--)-noradrenaline in human atrium. Br J Clin Pharmacol. 1996 Aug;42(2):217-23. [PubMed:8864321]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein homodimerization activity
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 ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Fuchsjager-Mayrl G, Markovic O, Losert D, Lucas T, Wachek V, Muller M, Schmetterer L: Polymorphism of the beta-2 adrenoceptor and IOP lowering potency of topical timolol in healthy subjects. Mol Vis. 2005 Sep 23;11:811-5. [PubMed:16205624]
  3. Rotmensch HH, Vlasses PH, Feinberg JA, Abrams WB, Ferguson RK: Comparisons of beta-adrenergic blocking properties of S- and R-timolol in humans. J Clin Pharmacol. 1993 Jun;33(6):544-8. [PubMed:8103526]
  4. Borger P, Hoekstra Y, Esselink MT, Postma DS, Zaagsma J, Vellenga E, Kauffman HF: Beta-adrenoceptor-mediated inhibition of IFN-gamma, IL-3, and GM-CSF mRNA accumulation in activated human T lymphocytes is solely mediated by the beta2-adrenoceptor subtype. Am J Respir Cell Mol Biol. 1998 Sep;19(3):400-7. [PubMed:9730867]
  5. Van der Graaf PH, Saxena PR, Shankley NP, Black JW: Exposure and characterization of the action of noradrenaline at dopamine receptors mediating endothelium-independent relaxation of rat isolated small mesenteric arteries. Br J Pharmacol. 1995 Dec;116(8):3237-42. [PubMed:8719802]
  6. Ferro A, Hall JA, Dickerson JE, Brown MJ: A prospective study of the effects of prolonged timolol therapy on alpha- and beta-adrenoceptor and angiotensin II receptor mediated responses in normal subjects. Br J Clin Pharmacol. 1997 Mar;43(3):301-8. [PubMed:9088585]
  7. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Enterobacteria phage T4
Pharmacological action
Unknown
General Function
Lysozyme activity
Specific Function
Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasin...
Gene Name
E
Uniprot ID
P00720
Uniprot Name
Endolysin
Molecular Weight
18691.385 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

Details
1. Cytochrome P450 2D6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase 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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. 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]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. 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]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Terao T, Hisanaga E, Sai Y, Tamai I, Tsuji A: Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as an absorption barrier. J Pharm Pharmacol. 1996 Oct;48(10):1083-9. [PubMed:8953513]

Drug created on June 13, 2005 07:24 / Updated on September 21, 2018 00:00