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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:48 UTC
HMDB IDHMDB14517
Secondary Accession NumbersNone
Metabolite Identification
Common NameTimolol
DescriptionTimolol is only found in individuals that have used or taken this drug. It is 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]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.
Structure
Thumb
Synonyms
ValueSource
Timolol maleateHMDB
Chemical FormulaC13H24N4O3S
Average Molecular Weight316.42
Monoisotopic Molecular Weight316.156911344
IUPAC Name1-(tert-butylamino)-3-{[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy}propan-2-ol
Traditional Name1-(tert-butylamino)-3-{[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy}propan-2-ol
CAS Registry Number26839-75-8
SMILES
CC(C)(C)NCC(O)COC1=NSN=C1N1CCOCC1
InChI Identifier
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
InChI KeyInChIKey=BLJRIMJGRPQVNF-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassAmines
Sub ClassTertiary amines
Direct ParentDialkylarylamines
Alternative Parents
Substituents
  • Dialkylarylamine
  • Alkyl aryl ether
  • Imidolactam
  • Oxazinane
  • Morpholine
  • 3-amino-1,2,5-thiadiazole
  • Heteroaromatic compound
  • Thiadiazole
  • Azole
  • Secondary alcohol
  • 1,2-aminoalcohol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Ether
  • Secondary aliphatic amine
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Adrenergic beta-Antagonists
  • Anti-Arrhythmia Agents
  • Antihypertensive Agents
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point201.5 - 202.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility2.69e-01 g/LNot Available
LogP1.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.27 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
Polarizability33.99 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Timolol Action PathwaySMP00659Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00373
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00373
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00373
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID5278
KEGG Compound IDC07141
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTimolol
NuGOwiki LinkHMDB14517
Metagene LinkHMDB14517
METLIN IDNot Available
PubChem Compound5478
PDB IDNot Available
ChEBI ID39465
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. InChem Data Sheet [Link]

Enzymes

General function:
Involved in monooxygenase 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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
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. Epub 2009 Nov 24. [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. 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. Epub 2009 Nov 24. [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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [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. [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. [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. [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. [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. [8864321 ]
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [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. [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. [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. [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. [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. [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. [10592235 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
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. [8953513 ]