General
Preferred name
timolol
Synonyms
S(-)-Timolol maleate ()
(S)-Timolol maleate ()
MK 950 ()
L-714,465 (Maleate) ()
TIMOLOL MALEATE ()
Timolol maleate salt ()
MK 950(S)-Timolol Maleate ()
TIMOLOL ANHYDROUS ()
(S)-Timolol (Maleate) ()
(S)-L-714,465 (maleate) ()
MK-950,(S)-Timolol Maleate ()
Timoptic ()
Timololi maleas ()
Istalol ()
Timoptic Xe ()
WP-934 ()
Timoptic In Ocudose ()
Blocadren ()
Aquanil ()
Ophtamolol ()
Timoptic-XE ()
Timolol hydrogen maleate salt ()
NSC-757351 ()
Timolol (as maleate) ()
Timolol maleate, s-enantiomer ()
Glau-Opt ()
Nyogel ()
Tiopex ()
Timolol hemihydrate ()
Betimol ()
Betim ()
Glaucol ()
Timolol (maleate) ()
P&D ID
PD002871
CAS
26921-17-5
60469-65-0
131628-37-0
26839-75-8
Tags
natural product
drug
available
Approved by
PMDA
FDA
First approval
1978
Drug Status
approved
Drug indication
High blood pressure
Anti-Adrenergic (beta-receptor)
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS Timolol, when administered by the ophthalmic route, rapidly reduces intraocular pressure. When administered in the tablet form, it reduces blood pressure, heart rate, and cardiac output, and decreases sympathetic activity.[A179506,A179509,A179512,L6727]. This drug has a fast onset of action, usually occurring within 20 minutes of the administration of an ophthalmic dose. Timolol maleate can exert pharmacological actions for as long as 24 hours if given in the 0.5% or 0.25% doses.[L6757]; ;
MOA Timolol competes with adrenergic neurotransmitters for binding to beta(1)-adrenergic receptors in the heart and the beta(2)-receptors in the vascular and bronchial smooth muscle. This leads to diminished actions of catecholamines, which normally bind to adrenergic receptors and exert sympathetic effects leading to an increase in blood pressure and heart rate.[A179521] Beta(1)-receptor blockade by timolol leads to a decrease in both heart rate and cardiac output during rest and exercise, and a decrease in both systolic and diastolic blood pressure.[A179524,A179527] In addition to this, a reduction in reflex orthostatic hypotension may also occur. The blockade of beta(2) receptors by timolol in the blood vessels leads to a decrease in peripheral vascular resistance, reducing blood pressure.[L6724,L6727,L6733]; ; The exact mechanism by which timolol reduces ocular pressure is unknown at this time, however, it likely decreases the secretion of aqueous humor in the eye.[L6730] According to one study, the reduction of aqueous humor secretion may occur through the decreased blood supply to the ciliary body resulting from interference with the active transport system or interference with prostaglandin biosynthesis.[A179515]
INDICATION Ophthalmic timolol is indicated for the treatment of increased intraocular pressure in patients with ocular hypertension or open-angle glaucoma. The oral form of this drug is used to treat high blood pressure.[L6724,L6727] In certain cases, timolol is used in the prevention of migraine headaches.[A179530,L6742]
ROE Timolol and its metabolites are mainly found excreted in the urine.[A179560]
TOXICITY The oral LD50 for timolol maleate is 1028 mg/kg in the rat and 1137 mg/kg in the mouse.[MSDS]; ; Symptoms of timolol overdose may include dizziness, headache, shortness of breath, bradycardia, in addition to bronchospasm. Sometimes, an overdose may lead to cardiac arrest. An overdose of timolol can be reversed with dialysis, however, patients with renal failure may not respond as well to dialysis treatment.[L6724]
METABOLISM Timolol is metabolized in the liver by the cytochrome P450 2D6 enzyme, with minor contributions from CYP2C19.[A179551,L6724] 15-20% of a dose undergoes first-pass metabolism.[A179560] Despite its relatively low first pass metabolism, timolol is 90% metabolized.[A179560] Four metabolites of timolol have been identified, with a hydroxy metabolite being the most predominant.[A179551]
ABSORPTION The systemic bioavailability of the ophthalmic eyedrop in one study of healthy volunteers was 78.0 ± 24.5% [A179539], indicating that caution must be observed when this drug is administered, as it may be significantly absorbed and have various systemic effects. Another study measured the bioavailability of timolol eyedrops to be 60% in healthy volunteers.[A179548]; ; The peak concentration of ophthalmic timolol in plasma, Cmax was about 1.14 ng/ml in most subjects within 15 minutes following the administration of timolol by the ophthalmic route. The mean area under the curve (AUC) was about 6.46 ng/ml per hour after intravenous injection and about 4.78 ng/ml per hour following eyedrop administration.[A179539]
HALF-LIFE Timolol half-life was measured at 2.9 ± 0.3 h hours in a clinical study of healthy volunteers.[A179560]
DESCRIPTION Marketed formulations may contain timolol maleate (PubChem CID 5281056). (GtoPdb)
DESCRIPTION Selective H1 inverse agonist (Tocris Bioactive Compound Library)
DESCRIPTION beta Adrenoceptor antagonist; antihypertensive; antiarrhythmic; antiglaucoma agent (LOPAC library)
DESCRIPTION β1 antagonist (Tocriscreen Total)
Cell lines
0
Organisms
1
Compound Sets
29
Axon Medchem Screening Library
1518
Cayman Chemical Bioactives
13974
ChEMBL Approved Drugs
CHEMBL1200870
CHEMBL499
ChEMBL Drugs
CHEMBL1200870
CHEMBL499
Concise Guide to Pharmacology 2017/18
565
Concise Guide to Pharmacology 2019/20
565
Concise Guide to Pharmacology 2021/22
565
Concise Guide to Pharmacology 2023/24
565
Drug Repurposing Hub
DrugBank
DB00373
DrugBank Approved Drugs
DB00373
DrugCentral
4061
DrugCentral Approved Drugs
4061
DrugMAP
DM3NXRU
DrugMAP Approved Drugs
DM3NXRU
Guide to Pharmacology
565
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL499
MedChem Express Bioactive Compound Library
HY-17380
NCATS Inxight Approved Drugs
5JKY92S7BR
NIH Clinical Collections (NCC)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
timolol-maleate
TargetMol Bioactive Compound Library
T0475
Tocris Bioactive Compound Library
0649
Tocriscreen Total
ZINC Tool Compounds
ZINC000000002176
External IDs
66
Properties
(calculated by RDKit )
Molecular Weight
316.16
Hydrogen Bond Acceptors
8
Hydrogen Bond Donors
2
Rotatable Bonds
6
Ring Count
2
Aromatic Ring Count
1
cLogP
0.5
TPSA
79.74
Fraction CSP3
0.85
Chiral centers
1.0
Largest ring
6.0
QED
0.79
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Selectivity
beta
Pathway
GPCR/G protein
Neuroscience
Neuronal Signaling
Target
??1-adrenergic receptor
??2-adrenergic receptor
ADRB1, ADRB2
ß blocker
Adrenergic Receptor
Primary Target
Adrenergic ?1 Receptors
MOA
Antagonist
Adrenergic Receptor antagonist
Indication
ocular hypertension, glaucoma
Therapeutic Class
Antiarrhythmic Agents
Source data