General
Preferred name
BRIMONIDINE
Synonyms
UK 14,304 ()
UK 14,304 tartrate ()
ICX5609012 ()
AGN190342 (tartrate) ()
UK 14304 (tartrate) ()
304 tartrate ()
AGN190342 tartrate ()
UK14304 tartrate ()
UK-14,304 ()
BRIMONIDINE TARTRATE ()
Brimonidine L-Tartrate ()
AGN190342 (tartrate)UK 14304 (tartrate)304 tartrate ()
Brominide tartrate ()
Brimonidine (tartrate) ()
UK 14304 ()
AGN190342 ()
UK 1434 Tartrate ()
Bromoxidine, UK 14304 ()
[3H]brimonidine ()
UK-14304 ()
NSC-318825 ()
UK-1430418 FREE BASE ()
AGN-190342 FREE BASE ()
Brimonidine d-tartrate ()
UK-14304-18 ()
AGN-190342-LF ()
OCU-300 ()
AGN-190342LF ()
Brymont ()
Mirvaso ()
Cd-07805 ()
OCU300 ()
UK-1430418 ()
Alphagan ()
Lumify ()
Qoliana ()
Bromoxidine tartrate ()
AGN 190342-LF ()
Alphagan p ()
Brimonidine-d4 ()
P&D ID
PD000495
CAS
70359-46-5
109826-56-4
79570-19-7
59803-98-4
1184971-51-4
Tags
available
drug
drug candidate
biased GPCR ligand
Approved by
PMDA
EMA
FDA
First approval
1996
Drug Status
approved
Drug indication
Discovery agent
Glaucoma/ocular hypertension
Adrenergic (ophthalmic)
Ocular hypertension
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
Brimonidine is an α-adrenergic receptor agonist (primarily α2).
MOA
In the eye, alpha-1 adrenoceptors play a role in vasoconstriction, mydriasis, eyelid retraction, and elevation of intraocular pressure (IOP) whereas alpha-2 adrenoceptors are responsible for IOP reduction via a complex Gi-coupled signaling cascade pathway. Activation of alpha-2 receptors leads to inhibition of adenylyl cyclase and reduction of cyclic AMP levels. As a result, there is a decrease in norpinephrine (NE) release at the synaptic junction, NE-induced stimulation of beta-2 adrenoceptors, and production of aqueous humor by the ciliary epithelium.[A178969] An elevated IOP is the most significant risk factor for developing glaucomatous optic neuropathy, which is associated with progressive visual field loss and functional disability if left untreated.[A179002] Regardless of the etiology of the disease, the aim of current therapies for glaucoma is to reduce IOP, as reduction of IOP significantly reduces the risk of progression of vision loss even when IOP is already within the normal range.[A36674] When administered ophthalmically, brimonidine is rapidly absorbed into the eye, acts as an agonist at ocular alpha-2 adrenoceptors and lowers IOP via a dual mechanism of action.[A178981] It is proposed that initial dosing of the drug causes a reduction in aqueous humour production and chronic dosing leads to an increase in uveoscleral outflow.[A179002] Brimonidine does not affect episcleral venous pressure.[A178969] By reducing IOP, brimonidine aims to reduce the likelihood of glaucomatous visual field loss in ocular hypertension, and slow the progression of visual field defect in established open-angle glaucoma.[A178951] When applied topically on skin, brimonidine reduces erythema through direct vasocontriction of small arteries and veins.[A178978] As brimonidine mediates a potent peripheral vasoconstrictive activity by selectively working on the alpha-2 adrenoceptors, the use of brimonidine is thought to be efficacious for the treatment of facial erythema of rosacea, which is thought to arise from vasomotor instability and abnormal vasodilation of the superficial cutaneous vasculature of the face.[A178984]
INDICATION
**Opthalmic**; ; Indicated for lowering intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension [label] as monotherapy or combination product with [brinzolamide].; ; **Topical**; ; Indicated for the treatment of persistent (non-transient) facial erythema of rosacea in adults 18 years of age or older.[L6535]
ROE
Brimonidine and its metabolites are predominantly eliminated via urinary excretion, with 74% of the total dose being found in the urine.[label]
TOXICITY
**LD50 and Overdose** ; ; Oral LD50 is 50 mg/kg in mice and 100 mg/kg in rats.[MSDS] While there is limited clinial data on brimonidine overdose in adults, some common symptoms from oral overdoses of alpha-2 adrenergic agonists include hypotension, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmias, miosis, apnoea, hypotonia, hypothermia, respiratory depression and seizure. [L6544] Treatment of an oral overdose includes supportive and symptomatic therapy. Cases of brimonidine overdose have been reported in neonates, infants, and pediatric patients receiving brimonidine tartrate as part of medical treatment of congenital glaucoma or by accidental oral ingestion. In these cases, children experienced symptoms consistent with previously reported oral overdoses of alpha-2 adrenergic agonists in young children.[L6544] ; ; **Nonclinical Toxicology**; ; At oral doses of up to 2.5 and 5 mg/kg/day in pregnant rats and rabbits, brimonidine was not shown to be teratogenic during gestation days 6 through 18. Findings from various _in vitro_ and _in vivo_ studies, including the Ames bacterial assay, CHO cell chromosomal aberration assay, and CD-1 mice studies, did not demonstrate any mutagenic or clastogenic potential of brimonidine.[label] There were no observable adverse effects on male or female fertility when tested at oral doses of up to 1 mg/kg, which is approximately 200 times the systemic exposure following the maximum recommended ophthalmic dose of 0.5% brimonidine.[label]; ; **Use in special populations**; ; Due to limited clinical data on the use of brimonidine pregnant or breastfeeding female patients, the use of brimonidine in these patients is generally not recommended and the use should be only considered after taking into account the benefit-to-risk ratio of continuing the drug therapy in these patients. In nursing mothers, the decision should be made whether to discontinue the drug or discontinue breastfeeding.[label] As the systemic absorption and elimination of brimonidine are not significantly affected by age, the use of brimonidine is considered safe in geriatric patients. In contrast, the use of brimonidine in infants under the age of 2 and pediatric patients under the age of 18 is strongly not recommended due to the reports of serious adverse events following ophthalmic administration of brimonidine in infants between the age of 28 days and 3 months.[L6544]
METABOLISM
Brimonidine is reported to be metabolized in the cornea. Brominidine that reaches the systemic circulation upon topical administration undergoes extensive hepatic metabolism mediated by hepatic aldehyde oxidases.[label]
ABSORPTION
Brimonidine readily penetrates the cornea following ocular administration [A178951] to reach pharmacologically active concentrations in the aqueous humor and ciliary body, the putative sites of its IOP-lowering activity.[A36674] Following ocular administration of 0.2% brimonidine solution, the peak plasma concentrations were achieved within 1 to 4 hours.[label]; ; In a clinical study of adult subjects with facial erythema of rosacea, brimonidine was cutaneously applied on facial skin in a repeated manner. While there was no drug accumulation in plasma, the highest peak plasma concentrations (Cmax) and AUC were 46 ± 62 pg/mL and 417 ± 264 pgxhr/mL, respectively.[L6544]
HALF-LIFE
Following ocular administration of 0.2% brimonidine solution, the systemic half-life was approximately 3 hours.[label]
DESCRIPTION
Brimonidine is an α-adrenoceptor agonist (primarily α2).
(GtoPdb)
DESCRIPTION
H1 agonist
(Tocris Bioactive Compound Library)
DESCRIPTION
alpha2 agonist
(Tocriscreen Plus)
DESCRIPTION
alpha2 Adrenoceptor agonist
(LOPAC library)
DESCRIPTION
α2 agonist
(Tocriscreen Total)
DESCRIPTION
α2 agonist. Water-soluble form of UK 14,304 (Cat. No. 0425)
(Tocriscreen Total)
DESCRIPTION
D2-like agonist (D2>D3>D4)
(Tocris Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
1
Compound Sets
37
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
BiasDB
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP Approved Drugs
DrugMatrix
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
Ki Database
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocriscreen Plus
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ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
79
Molecular Weight
291.01
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
2
Rotatable Bonds
1
Ring Count
3
Aromatic Ring Count
2
cLogP
1.76
TPSA
62.2
Fraction CSP3
0.18
Chiral centers
0.0
Largest ring
6.0
QED
0.84
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
7-TM Receptors
Selectivity
alpha2
Pathway
GPCR/G protein
Neuroscience
Neuronal Signaling
Target
??2A-adrenergic receptor
¦Á2A-adrenergic receptor
ADRA2A, ADRA2B, ADRA2C
a2 agonist
Adrenergic Receptor
Primary Target
Adrenergic ?2 Receptors
MOA
Adrenergic Receptor agonist
Agonist
Indication
intraocular pressure, glaucoma, ocular hypertension
Source data
