Identification

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Name
Brimonidine
Accession Number
DB00484  (APRD00034)
Type
Small Molecule
Groups
Approved
Description

Brimonidine is an alpha-adrenergic agonist and 2-imidazoline derivative that was first introduced in 1996.3 It is considered to be a third generation alpha-2 aadrenergic receptor agonist, since it displays preferential binding at alpha-2 adrenoceptors over alpha-1 receptors.11 Brimonidine displays a higher selectivity toward the alpha-2 adrenergic receptors than clonidine or apraclonidine, which are also alpha-2 adrenergic agonists.6 Alpha-2 adrenergic agonists are members of the ocular hypotensive agent drug class that are used in the chronic treatment of glaucoma. Early treatment and management of glaucoma, which predominantly involves the lowering of intraocular pressure, is critical since glaucoma is considered to be a common cause of blindness worldwide.2,6

Ophthalmically, brimonidine is used to lower intraocular pressure by reducing aqueous humor production and increasing uveoscleral outflow. Because it is oxidately stable, brimonidine is associated with fewer reports of ocular allergic reactions compared to other alpha-2 adrenergic agonists.6 The ophthalmic solution of brimonidine was first approved by the FDA in 1996 as Alphagan Label and brimonidine is the only selective alpha-adrenergic receptor agonist approved for chronic treatment in glaucoma.7 Brimonidine is also found in ophthalmic solutions in combination with brinzolamide under the market name Simbrinza for the reduction in intraocular pressure. Unlike nonselective beta-blockers used in ocular hypertension, brimonidine is not associated with significantly adverse cardiopulmonary side effects.1 Thus brimonidine is an effective and safe alternative to beta-blockers, in patients with, or at high risk for, cardiopulmonary disease.2 The topical form of brimonidine was approved by the FDA in August 2013 for the symptomatic treatment of persistent facial erythema of rosacea in adults. It is marketed under the brand name Mirvaso.13 Brimonidine is the first topical treatment approved for facial erythema of rosacea.8

Structure
Thumb
Synonyms
  • 5-Bromo-6-(2-imidazolin-2-ylamino)quinoxaline
  • Brimonidina
  • Brimonidine
  • Brimonidinum
  • Bromoxidine
External IDs
AGN-190342 / UK-14304
Product Ingredients
IngredientUNIICASInChI Key
Brimonidine tartrate4S9CL2DY2H70359-46-5QZHBYNSSDLTCRG-LREBCSMRSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AlphaganLiquidOphthalmicAllergan1997-12-02Not applicableCanada
Alphagan PSolution / drops1 mg/1mLOphthalmicPhysicians Total Care, Inc.2013-03-08Not applicableUs
Alphagan PSolution / drops1.5 mg/1mLOphthalmicPhysicians Total Care, Inc.2002-10-16Not applicableUs
Alphagan PSolution0.15 %OphthalmicAllergan2003-11-05Not applicableCanada
Alphagan PSolution / drops1.5 mg/1mLOphthalmicAllergan, Inc.2001-07-10Not applicableUs
Alphagan PSolution / drops1 mg/1mLOphthalmicAllergan, Inc.2006-01-25Not applicableUs
BrimonidineSolution0.2 %OphthalmicPharmascience IncNot applicableNot applicableCanada
Brimonidine OphthalmicSolutionOphthalmicPharmel IncNot applicableNot applicableCanada
Brimonidine PSolutionOphthalmicAa Pharma Inc2008-07-15Not applicableCanada
Brimonidine TartrateSolution1.5 mg/1mLOphthalmicPhysicians Total Care, Inc.2009-12-22Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-brimonidineSolutionOphthalmicApotex Corporation2005-06-02Not applicableCanada
BrimonidineSolution / drops2 mg/1mLOphthalmicAkorn2006-09-07Not applicableUs
BrimonidineSolution / drops2 mg/1mLOphthalmicA-S Medication Solutions2006-09-072017-11-17Us
Brimonidine TartrateSolution / drops2 mg/1mLOphthalmicSomerset Therapeutics, Llc2019-03-23Not applicableUs
Brimonidine TartrateSolution / drops2 mg/1mLOphthalmicPacific Pharma2003-04-102017-12-29Us
Brimonidine TartrateSolution / drops2 mg/1mgOphthalmicOsmotica Pharmaceutical Corp.2015-01-01Not applicableUs
Brimonidine TartrateSolution / drops2 mg/1mLOphthalmicSomerset Therapeutics, Llc2019-03-23Not applicableUs
Brimonidine TartrateSolution / drops2 mg/1mLOphthalmicPhysicians Total Care, Inc.2011-07-25Not applicableUs
Brimonidine TartrateSolution2 mg/1mLOphthalmicSandoz2003-09-17Not applicableUs
Brimonidine TartrateSolution / drops2 mg/1mLOphthalmicSomerset Therapeutics, Llc2019-03-23Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LUMIFY Redness Reliever Eye DropsSolution / drops0.25 mg/1mLOphthalmicBausch & Lomb Incorporated2017-12-22Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
CombiganBrimonidine tartrate (2 mg/1mL) + Timolol maleate (5 mg/1mL)Solution / dropsOphthalmicPhysicians Total Care, Inc.2011-08-29Not applicableUs
CombiganBrimonidine tartrate (0.2 %) + Timolol (0.5 %)SolutionOphthalmicAllergan2003-12-11Not applicableCanada
CombiganBrimonidine tartrate (2 mg/1mL) + Timolol maleate (5 mg/1mL)Solution / dropsOphthalmicAllergan, Inc.2007-11-14Not applicableUs
SimbrinzaBrimonidine tartrate (2 mg/1mL) + Brinzolamide (10 mg/1mL)Suspension / dropsOphthalmicALCON LABORATORIES, INC.2013-05-01Not applicableUs
SimbrinzaBrimonidine tartrate (0.2 %) + Brinzolamide (1 %)SuspensionOphthalmicNovartis2015-02-17Not applicableCanada
SimbrinzaBrimonidine tartrate (2 mg/ml) + Brinzolamide (10 mg/ml)Suspension / dropsOphthalmicNovartis Europharm Limited2014-07-18Not applicableEu
SimbrinzaBrimonidine tartrate (2 mg/ml) + Brinzolamide (10 mg/ml)Suspension / dropsOphthalmicNovartis Europharm Limited2014-07-18Not applicableEu
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Brim-Dor PFBrimonidine tartrate (1.5 mg/1mL) + Dorzolamide hydrochloride (20 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Brimonidine Tartrate 0.25% / Ivermectin 1% / Metronidazole 1% / Niacinamide 4%Brimonidine tartrate (0.25 g/100g) + Ivermectin (1 g/100g) + Metronidazole (1 g/100g) + Nicotinamide (4 g/100g)GelTopicalSincerus Florida, LLC2019-05-16Not applicableUs
Brimonidine Tartrate 0.25% / Potassium Azeloyl Diglycinate 8%Brimonidine tartrate (0.25 g/100g)GelTopicalSincerus Florida, LLC2019-05-16Not applicableUs
Tim-Brim-Dor PFBrimonidine tartrate (1.5 mg/1mL) + Dorzolamide hydrochloride (20 mg/1mL) + Timolol maleate (5 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Tim-Brim-Dor-LatBrimonidine tartrate (1.5 mg/1mL) + Dorzolamide hydrochloride (20 mg/1mL) + Latanoprost (0.05 mg/1mL) + Timolol maleate (5 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Categories
UNII
E6GNX3HHTE
CAS number
59803-98-4
Weight
Average: 292.135
Monoisotopic: 291.011957992
Chemical Formula
C11H10BrN5
InChI Key
XYLJNLCSTIOKRM-UHFFFAOYSA-N
InChI
InChI=1S/C11H10BrN5/c12-9-7(17-11-15-5-6-16-11)1-2-8-10(9)14-4-3-13-8/h1-4H,5-6H2,(H2,15,16,17)
IUPAC Name
5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine
SMILES
BrC1=C(NC2=NCCN2)C=CC2=NC=CN=C12

Pharmacology

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.13

Associated Conditions
Pharmacodynamics

Brimonidine is a highly selective alpha-2 adrenergic receptor agonist that is 1000-fold more selective for the alpha2-adrenergic receptor than the alpha1-adrenergic receptor.15 This characteristic gives the drug some therapeutic advantages, since it reduces the risk of systemic side effects, such as systemic hypotension, bradycardia, and sedation. In addition, there is a reduction in the risk for developing alpha-1 mediated ocular unwanted effects, such as conjunctival blanching, mydriasis, and eyelid retraction.11 However, despite high alpha-2 receptor specificity, brimonidine may still produce alpha-1 adrenoceptor-mediated ocular effects, such as conjunctival vasoconstriction.6 Brimonidine has a peak ocular hypotensive effect occurring at two hours post-dosing.Label In a randomized, double-blind clinical study, ocular administration of 0.2% brimonidine in healthy volunteers resulted in a 23% reduction of mean intraocular pressure from baseline at 3 hours following administration.3 In comparative studies consisting of patients with open-angle glaucoma or ocular hypertension, the ocular hypotensive effect of brimonidine was maintained during treatment periods of up to 1 year.1

Brimonidine mediates vasoconstrictive effects and it was shown to exhibit anti-inflammatory properties in ex vivo human skin model and in vivo inflammation models.12 In a clinial trials consisting of adults with moderate to severe facial erythema of rosacea, brimonidine was shown to improve the extent of redness at 3 hours after application, compared to placebo.15 It was shown to be a potent vasoconstrictor of human subcutaneous vessels with a diameter of less than 200 µm. In in vivo mouse inflammation models, brimonidine displayed anti-inflammatory properties by inhibiting edema.8 In a randomized, double-blind study, brimonidine reduced erythema for the 12 hours of the study in a dose-dependent manner.8

When adminsitered systemically, brimonidine was shown to cause cardiovascular effects by decreasing blood pressure, decreasing heart and respiratory rate, and prolonging the PR interval in the electrocardiogram. This is due to the targeting of adrenoceptors by the drug.4,5 Although the clinical significance has not been established, there is evidence that brimonidine exhibits neuroprotective activity in experimental models of cerebral ischemia and optic nerve injury.6 In vitro studies show that brimonidine mediated protective effects on neuronal cells from kainate acid insult and on cultured retinal ganglion cells from glutamate-induced cytotoxicity, which is a possible mediator of secondary neuronal degeneration in human glaucoma. Neuroprotective actions of brimonidine were also demonstrated in rat models of acute retinal ischemia and chronic IOP elevation. It has been proposed that brimonidine may exert neuroprotective effects on the retina and optic nerve by enhancing intrinsic retinal ganglion cell survival mechanisms and/or induction of neuronal survival factors, such as bFGF.3 However, further investigations are needed to conclude on these possible therapeutic benefits of the drug.

Mechanism of action

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.6 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.11 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.7 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.9 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.11 Brimonidine does not affect episcleral venous pressure.6 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.3 When applied topically on skin, brimonidine reduces erythema through direct vasocontriction of small arteries and veins.8 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.10

TargetActionsOrganism
AAlpha-2A adrenergic receptor
agonist
Humans
AAlpha-2B adrenergic receptor
agonist
Humans
AAlpha-2C adrenergic receptor
agonist
Humans
Additional Data Available
Adverse Effects

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Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

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Absorption

Brimonidine readily penetrates the cornea following ocular administration 3 to reach pharmacologically active concentrations in the aqueous humor and ciliary body, the putative sites of its IOP-lowering activity.7 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.15

Volume of distribution

The volume of distribution of brimonidine has not been established. In animal studies, brimonidine was shown to cross the placenta and enter into the fetal circulation to a limited extent.Label As its lipophilicity is relatively low, brimonidine is not reported to easily cross the blood-brain barrier.3

Protein binding

The protein binding of brimonidine has not been studied.

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

Route of elimination

Brimonidine and its metabolites are predominantly eliminated via urinary excretion, with 74% of the total dose being found in the urine.Label

Half life

Following ocular administration of 0.2% brimonidine solution, the systemic half-life was approximately 3 hours.Label

Clearance

The apparent clearance has not been studied. However, the systemic clearance of brimonidine is reported to be rapid.7 Approximately 87% of the total radioactive dose of brimonidine was shown to be eliminated within 120 hours following oral administration.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. 15 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.15

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.15

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
2,5-Dimethoxy-4-ethylthioamphetamineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleBrimonidine may increase the central nervous system depressant (CNS depressant) activities of 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe metabolism of Brimonidine can be decreased when combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AcebutololBrimonidine may increase the antihypertensive activities of Acebutolol.
AcepromazineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Acepromazine.
AceprometazineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Aceprometazine.
AcetazolamideBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Acetazolamide.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. Adkins JC, Balfour JA: Brimonidine. A review of its pharmacological properties and clinical potential in the management of open-angle glaucoma and ocular hypertension. Drugs Aging. 1998 Mar;12(3):225-41. doi: 10.2165/00002512-199812030-00005. [PubMed:9534022]
  2. Cantor LB, Burke J: Brimonidine. Expert Opin Investig Drugs. 1997 Aug;6(8):1063-83. doi: 10.1517/13543784.6.8.1063 . [PubMed:15989664]
  3. Cantor LB: The evolving pharmacotherapeutic profile of brimonidine, an alpha 2-adrenergic agonist, after four years of continuous use. Expert Opin Pharmacother. 2000 May;1(4):815-34. doi: 10.1517/14656566.1.4.815 . [PubMed:11249518]
  4. Stewart WC, Stewart JA, Jackson AL: Cardiovascular effects of timolol maleate, brimonidine or brimonidine/timolol maleate in concomitant therapy. Acta Ophthalmol Scand. 2002 Jun;80(3):277-81. [PubMed:12059866]
  5. Suwanwipat S, Buranakarl C, Chaiyabutr N: Effects of brimonidine ingestion on cardiovascular responses and renal function in conscious dogs. Vet Res Commun. 2007 Apr;31(3):323-34. doi: 10.1007/s11259-006-3414-1. Epub 2006 Dec 28. [PubMed:17195055]
  6. Greenfield DS, Liebmann JM, Ritch R: Brimonidine: a new alpha2-adrenoreceptor agonist for glaucoma treatment. J Glaucoma. 1997 Aug;6(4):250-8. [PubMed:9264305]
  7. Cantor LB: Brimonidine in the treatment of glaucoma and ocular hypertension. Ther Clin Risk Manag. 2006 Dec;2(4):337-46. [PubMed:18360646]
  8. Jackson JM, Knuckles M, Minni JP, Johnson SM, Belasco KT: The role of brimonidine tartrate gel in the treatment of rosacea. Clin Cosmet Investig Dermatol. 2015 Oct 23;8:529-38. doi: 10.2147/CCID.S58920. eCollection 2015. [PubMed:26566370]
  9. Toris CB, Gleason ML, Camras CB, Yablonski ME: Effects of brimonidine on aqueous humor dynamics in human eyes. Arch Ophthalmol. 1995 Dec;113(12):1514-7. [PubMed:7487618]
  10. Benkali K, Leoni M, Rony F, Bouer R, Fernando A, Graeber M, Wagner N: Comparative pharmacokinetics and bioavailability of brimonidine following ocular and dermal administration of brimonidine tartrate ophthalmic solution and gel in patients with moderate-to-severe facial erythema associated with rosacea. Br J Dermatol. 2014 Jul;171(1):162-9. doi: 10.1111/bjd.12881. Epub 2014 Jul 16. [PubMed:24506775]
  11. Galanopoulos A, Goldberg I: Clinical efficacy and neuroprotective effects of brimonidine in the management of glaucoma and ocular hypertension. Clin Ophthalmol. 2009;3:117-22. Epub 2009 Jun 2. [PubMed:19668554]
  12. Piwnica D, Pathak A, Schafer G, Docherty JR: In Vitro Safety Pharmacology Profiling of Topical alpha-Adrenergic Agonist Treatments for Erythema of Rosacea. Drugs R D. 2018 Mar;18(1):87-90. doi: 10.1007/s40268-018-0227-y. [PubMed:29374829]
  13. MIRVASO (brimonidine) topical gel - FDA Label [Link]
  14. Brimonidine (brimonidine tartrate) ophthalmic solution - Product Monograph [Link]
  15. Mirvaso (brimonidine) topical gel - EU Summary of Product Characteristics [Link]
External Links
Human Metabolome Database
HMDB0014627
KEGG Drug
D07540
KEGG Compound
C07886
PubChem Compound
2435
PubChem Substance
46507305
ChemSpider
2341
BindingDB
34572
ChEBI
3175
ChEMBL
CHEMBL844
Therapeutic Targets Database
DAP000280
PharmGKB
PA448665
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Brimonidine
ATC Codes
D11AX21 — BrimonidineS01EA05 — Brimonidine
AHFS Codes
  • 52:40.04 — Alpha-adrenergic Agonists
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
FDA label
Download (174 KB)
MSDS
Download (285 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentAlcohol-Related Disorders / Aldehyde Dehydrogenase Deficiency / Flushing1
0RecruitingTreatmentPresbyopia / Pseudophakia1
1CompletedBasic ScienceVitrectomy therapy1
1CompletedPreventionIntraocular Pressure1
1CompletedScreeningHyperemia1
1CompletedTreatmentEye Diseases / Glaucoma / Ocular Hypertension1
1CompletedTreatmentGlaucoma and Ocular Hypertension1
1RecruitingTreatmentGlaucoma1
1, 2CompletedTreatmentRetinitis Pigmentosa (RP)1
1, 2TerminatedTreatmentDry Eye / Graft versus host disease in eye / Meibomian Gland Dysfunction (MGD)1
2CompletedNot AvailableMacular Degeneration / Macular Edema / Retinopathy, Diabetic1
2CompletedPreventionConjunctivitis, Seasonal Allergic1
2CompletedTreatmentAge Related Macular Degeneration (ARMD) / Retinopathy, Diabetic1
2CompletedTreatmentGlaucoma, Primary Open Angle (POAG)1
2CompletedTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
2CompletedTreatmentGlaucoma / Ocular Hypertension1
2CompletedTreatmentMacular Degeneration1
2CompletedTreatmentOcular Hypertension1
2CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)1
2CompletedTreatmentOcular Redness1
2CompletedTreatmentOpen Angle Glaucoma (OAG)1
2CompletedTreatmentOpen-angle Glaucoma (OAG)1
2CompletedTreatmentRhegmatogenous Macula-off Retinal Detachment1
2CompletedTreatmentRosacea Subtype 1 (Erythematotelangiectatic)1
2Not Yet RecruitingNot AvailableHealthy Volunteers1
2RecruitingTreatmentDry Eye1
2RecruitingTreatmentIntraoperatice floppy iris syndrome (IFIS)1
2TerminatedTreatmentDry Macular Degeneration / Macular Degeneration1
2TerminatedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)1
2TerminatedTreatmentHand-and-foot syndrome1
2Unknown StatusTreatmentGlaucoma1
2, 3CompletedPreventionRetinopathy, Diabetic1
3CompletedOtherHyperemia1
3CompletedTreatmentAcne Rosacea2
3CompletedTreatmentAcne Rosacea / Erythemas2
3CompletedTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
3CompletedTreatmentGlaucoma / Ocular Hypertension5
3CompletedTreatmentHyperemia1
3CompletedTreatmentOcular Hypertension2
3CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)8
3Not Yet RecruitingTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
3RecruitingTreatmentBrimonidine Tartrate / Graft Versus Host Disease (GVHD) / Graft versus host disease in eye / Lubricant Eye Drops / Ocular Surface Disease / OGVHD / Ophthalmic Solutions1
3RecruitingTreatmentDry Eye1
3RecruitingTreatmentGlaucoma, Primary Open Angle (POAG)1
3RecruitingTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)1
3TerminatedTreatmentCapillary Malformations1
3Unknown StatusTreatmentCorneal Edema / Visual Acuity1
3Unknown StatusTreatmentGlaucoma1
3WithdrawnTreatmentGlaucoma / Ocular Hypertension1
4Active Not RecruitingDiagnosticGlaucoma, Primary Open Angle (POAG) / Glaucoma; Drugs / Normal Tension Glaucoma1
4CompletedNot AvailableGlaucoma1
4CompletedOtherAcne Rosacea1
4CompletedPreventionIntraocular Pressure1
4CompletedPreventionOcular Hypertension / Posterior Capsule Opacification1
4CompletedTreatmentAcne Rosacea3
4CompletedTreatmentChronic Persistent Vascular Facial Erythema1
4CompletedTreatmentGlaucoma8
4CompletedTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
4CompletedTreatmentGlaucoma / Ocular Hypertension6
4CompletedTreatmentNormal Tension Glaucoma / Open-angle Glaucoma (OAG)1
4CompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG)2
4CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)7
4CompletedTreatmentOpen-angle Glaucoma (OAG)1
4CompletedTreatmentPhysiology, Ocular / Regional Blood Flow1
4CompletedTreatmentProstate Cancer1
4CompletedTreatmentTelangiectasias1
4Not Yet RecruitingTreatmentDroopy Eyelid / Glaucoma / Glaucoma, Primary Open Angle (POAG) / Glaucoma; Drugs / Open-angle Glaucoma (OAG) / Ptosis1
4RecruitingTreatmentAcne Rosacea1
4RecruitingTreatmentEyelid Droop1
4RecruitingTreatmentGlaucoma1
4TerminatedTreatmentAngle-Closure Glaucoma1
4TerminatedTreatmentGlaucoma1
4TerminatedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)1
4Unknown StatusEducational/Counseling/TrainingGlaucoma1
4Unknown StatusTreatmentNormal Tension Glaucoma1
4WithdrawnSupportive CareRelapsing Remitting Multiple Sclerosis (RRMS)1
Not AvailableCompletedNot AvailableAcne Rosacea1
Not AvailableCompletedNot AvailableGlaucoma Due to Silicon Oil / Rhegmatogenous Retinal Detachments / Toxic Effect of Silicone1
Not AvailableCompletedNot AvailableHealthy Volunteers1
Not AvailableCompletedNot AvailableOcular Hypertension / Open-angle Glaucoma (OAG)1
Not AvailableCompletedBasic ScienceGlaucoma1
Not AvailableCompletedPreventionIntraocular Pressure Change in Intravitreal Injection1
Not AvailableCompletedPreventionPost-Injection Intraocular Pressure Spikes1
Not AvailableCompletedTreatmentCataracts1
Not AvailableCompletedTreatmentCataracts / Intraocular Pressure1
Not AvailableCompletedTreatmentGlaucoma2
Not AvailableCompletedTreatmentGlaucoma / Ocular Hypertension2
Not AvailableCompletedTreatmentIntraocular Pressure1
Not AvailableCompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG) / Pseudoexfoliation Syndrome1
Not AvailableCompletedTreatmentPhysiology, Ocular / Retina1
Not AvailableCompletedTreatmentPrimary Vascular Dysregulation1
Not AvailableNot Yet RecruitingPreventionOcular Hypertension1
Not AvailableNot Yet RecruitingTreatmentGlaucoma / Glaucoma; Drugs1
Not AvailableRecruitingTreatmentComplications of Diabetes Mellitus1
Not AvailableTerminatedTreatmentErythema and Flushing Associated With Rosacea1
Not AvailableUnknown StatusNot AvailableImpact of Brimonidine on the Cornea1
Not AvailableUnknown StatusTreatmentGlaucoma / Ocular Hypertension1
Not AvailableWithdrawnBasic ScienceGlaucoma1
Not AvailableWithdrawnDiagnosticIntraocular Pressure / Physiology, Ocular1

Pharmacoeconomics

Manufacturers
  • Allergan inc
  • Allergan
  • Akorn inc
  • Alcon inc
  • Alcon research ltd
  • Bausch and lomb pharmaceuticals inc
  • Sandoz canada inc
  • Teva parenteral medicines inc
  • Allergan, Inc
Packagers
  • Akorn Inc.
  • Alcon Laboratories
  • Allergan Inc.
  • Bausch & Lomb Inc.
  • Falcon Pharmaceuticals Ltd.
  • Ivax Pharmaceuticals
  • Pacific Pharma Lp
  • Physicians Total Care Inc.
  • Stat Rx Usa
Dosage forms
FormRouteStrength
LiquidOphthalmic
SolutionOphthalmic0.15 %
Solution / dropsOphthalmic1 mg/1mL
Solution / dropsOphthalmic1.5 mg/1mL
SolutionOphthalmic0.2 %
SolutionOphthalmic1.5 mg/1mL
SolutionOphthalmic2 mg/1mL
Solution / dropsOphthalmic2 mg/1mL
Solution / dropsOphthalmic2 mg/1mg
Solution / dropsOphthalmic2.0 mg/1mL
GelTopical
GelTopical0.25 g/100g
SolutionOphthalmic
Solution / dropsOphthalmic
Solution / dropsOphthalmic0.25 mg/1mL
GelCutaneous3 mg/g
GelTopical5 mg/1g
GelTopical
SolutionOphthalmic
SuspensionOphthalmic
Suspension / dropsOphthalmic
Prices
Unit descriptionCostUnit
Alphagan P 15ml Bottle .15% 15ml Bottle228.5USD bottle
Brimonidine Tartrate 0.15% Solution 15ml Bottle218.5USD bottle
Alphagan P 0.1% Solution 15ml Bottle208.94USD bottle
Alphagan P 10ml Bottle .15% 10ml Bottle152.32USD bottle
Brimonidine Tartrate 0.15% Solution 10ml Bottle145.65USD bottle
Alphagan P 0.1% Solution 10ml Bottle143.97USD bottle
Alphagan P 5ml Bottle .15% 5ml Bottle79.52USD bottle
Brimonidine Tartrate 0.15% Solution 5ml Bottle72.85USD bottle
Brimonidine Tartrate 0.2% Solution 10ml Bottle67.85USD bottle
Brimonidine Tartrate 0.2% Solution 15ml Bottle56.88USD bottle
Brimonidine Tartrate 0.2% Solution 5ml Bottle33.96USD bottle
Brimonidine tartrate 0.15% drp29.82USD ml
Alphagan p 0.15% eye drops14.65USD ml
Alphagan p 0.1% drops13.85USD ml
Brimonidine 0.2% eye drop6.53USD ml
Alphagan 0.2 % Solution3.72USD ml
Apo-Brimonidine 0.2 % Solution2.08USD ml
Pms-Brimonidine 0.2 % Solution2.08USD ml
Ratio-Brimonidine 0.2 % Solution2.08USD ml
Sandoz Brimonidine 0.2 % Solution2.08USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5424078No1995-06-132012-06-13Us
CA2173974No2006-05-022014-09-19Canada
CA2225626No2002-09-032016-06-17Canada
US9295641Yes2016-03-292022-01-10Us
US6627210Yes2003-09-302022-01-18Us
US6673337Yes2004-01-062022-01-26Us
US6562873Yes2003-05-132022-01-10Us
US6641834Yes2003-11-042022-01-28Us
US7030149No2006-04-182022-04-19Us
US7320976No2008-01-222022-04-19Us
US7642258No2010-01-052022-04-19Us
US8133890No2012-03-132022-04-19Us
US8354409No2013-01-152022-04-19Us
US8748425No2014-06-102022-04-19Us
US7323463No2008-01-292023-01-19Us
US7265117No2007-09-042025-08-19Us
US8858961Yes2014-10-142024-03-02Us
US6316441No2001-11-132019-12-07Us
US9044484No2015-06-022030-10-30Us
US8410102No2013-04-022025-05-24Us
US8053427No2011-11-082031-06-13Us
US7439241No2008-10-212025-08-25Us
US8513247No2013-08-202031-03-25Us
US8426410No2013-04-232025-05-24Us
US8513249No2013-08-202031-03-25Us
US8859551No2014-10-142024-05-25Us
US8231885No2012-07-312025-05-24Us
US8163725No2012-04-242031-06-13Us
US9474751No2016-10-252022-04-19Us
US9687443Yes2017-06-272022-01-10Us
US9421265No2016-08-232030-06-17Us
US9770453No2017-09-262022-04-19Us
US9861631No2018-01-092031-03-25Us
US8293742No2012-10-232030-07-14Us
US9861632No2018-01-092031-03-25Us
US9907801No2018-03-062022-04-19Us
US9907802No2018-03-062022-04-19Us
US10201517No2019-02-122031-06-13Us
US10307368No2001-07-102021-07-10Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)207.5 °CSandoz Canada Product Monograph
water solubility34 mg/mLSandoz Canada Product Monograph
pKa7.78Sandoz Canada Product Monograph
Predicted Properties
PropertyValueSource
Water Solubility0.154 mg/mLALOGPS
logP1.27ALOGPS
logP1.37ChemAxon
logS-3.3ALOGPS
pKa (Strongest Basic)8.32ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area62.2 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity68.49 m3·mol-1ChemAxon
Polarizability25.74 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.978
Blood Brain Barrier+0.717
Caco-2 permeable+0.5435
P-glycoprotein substrateSubstrate0.7017
P-glycoprotein inhibitor INon-inhibitor0.5688
P-glycoprotein inhibitor IIInhibitor0.5951
Renal organic cation transporterInhibitor0.8266
CYP450 2C9 substrateNon-substrate0.8403
CYP450 2D6 substrateNon-substrate0.7533
CYP450 3A4 substrateNon-substrate0.5617
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.6898
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7044
Ames testNon AMES toxic0.8222
CarcinogenicityNon-carcinogens0.9446
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.0196 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8093
hERG inhibition (predictor II)Non-inhibitor0.6711
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-0190000000-49c10e93a1977cbe01da

Taxonomy

Description
This compound belongs to the class of organic compounds known as quinoxalines. These are compounds containing a quinoxaline moiety, a bicyclic heterocycle made up of a benzene ring fused to a pyrazine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Quinoxalines
Alternative Parents
Pyrazines / Benzenoids / Aryl bromides / Imidazolines / Heteroaromatic compounds / Guanidines / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
Quinoxaline / Aryl bromide / Aryl halide / Pyrazine / Benzenoid / 2-imidazoline / Heteroaromatic compound / Guanidine / Azacycle / Carboximidamide
show 9 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
imidazoles, quinoxaline derivative, secondary amine (CHEBI:3175)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Rauly I, Ailhaud M, Wurch T, Pauwels PJ: alpha(2A)-adrenoceptor: G(alphai1) protein-mediated pertussis toxin-resistant attenuation of G(s) coupling to the cyclic AMP pathway. Biochem Pharmacol. 2000 Jun 15;59(12):1531-8. [PubMed:10799649]
  2. Wikberg-Matsson A, Simonsen U: Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries. Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2049-55. [PubMed:11481271]
  3. Meana JJ, Barturen F, Garro MA, Garcia-Sevilla JA, Fontan A, Zarranz JJ: Decreased density of presynaptic alpha 2-adrenoceptors in postmortem brains of patients with Alzheimer's disease. J Neurochem. 1992 May;58(5):1896-904. [PubMed:1373179]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Epinephrine binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
References
  1. Trendelenburg AU, Philipp M, Meyer A, Klebroff W, Hein L, Starke K: All three alpha2-adrenoceptor types serve as autoreceptors in postganglionic sympathetic neurons. Naunyn Schmiedebergs Arch Pharmacol. 2003 Dec;368(6):504-12. Epub 2003 Nov 11. [PubMed:14610637]
  2. Bohmann C, Schollmeyer P, Rump LC: Methoxamine inhibits noradrenaline release through activation of alpha 1- and alpha 2-adrenoceptors in rat isolated kidney: involvement of purines and prostaglandins. Naunyn Schmiedebergs Arch Pharmacol. 1993 Mar;347(3):273-9. [PubMed:8097565]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
References
  1. Trendelenburg AU, Philipp M, Meyer A, Klebroff W, Hein L, Starke K: All three alpha2-adrenoceptor types serve as autoreceptors in postganglionic sympathetic neurons. Naunyn Schmiedebergs Arch Pharmacol. 2003 Dec;368(6):504-12. Epub 2003 Nov 11. [PubMed:14610637]
  2. Orito K, Kishi M, Imaizumi T, Nakazawa T, Hashimoto A, Mori T, Kambe T: alpha(2)-adrenoceptor antagonist properties of OPC-28326, a novel selective peripheral vasodilator. Br J Pharmacol. 2001 Oct;134(4):763-70. [PubMed:11606316]
  3. Zhang W, Ordway GA: The alpha2C-adrenoceptor modulates GABA release in mouse striatum. Brain Res Mol Brain Res. 2003 Apr 10;112(1-2):24-32. [PubMed:12670699]
  4. Prinster SC, Holmqvist TG, Hall RA: Alpha2C-adrenergic receptors exhibit enhanced surface expression and signaling upon association with beta2-adrenergic receptors. J Pharmacol Exp Ther. 2006 Sep;318(3):974-81. Epub 2006 Jun 6. [PubMed:16757535]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine dehydrogenase activity
Specific Function
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal...
Gene Name
AOX1
Uniprot ID
Q06278
Uniprot Name
Aldehyde oxidase
Molecular Weight
147916.735 Da
References
  1. Acheampong AA, Chien DS, Lam S, Vekich S, Breau A, Usansky J, Harcourt D, Munk SA, Nguyen H, Garst M, Tang-Liu D: Characterization of brimonidine metabolism with rat, rabbit, dog, monkey and human liver fractions and rabbit liver aldehyde oxidase. Xenobiotica. 1996 Oct;26(10):1035-55. [PubMed:8905918]

Drug created on June 13, 2005 07:24 / Updated on December 09, 2019 19:14