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Identification
Name Brimonidine
Accession Number DB00484 (APRD00034)
Type small molecule
Groups approved
Description

Brimonidine is a drug used to treat glaucoma. It acts via decreasing aqueous humor synthesis. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Brimonidine tartrate
  • Bromoxidine
Brand names
  • Alphagan
  • Alphagan P
Brand name mixtures Not Available
Categories
  • Antihypertensive Agents
  • EENT Drugs
  • Adrenergic alpha-Agonists
CAS number 59803-98-4
Weight Average: 292.135
Monoisotopic: 291.011957992
Chemical Formula C11H10BrN5
InChI Key InChIKey=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)
Plain Text
IUPAC Name
5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine
SMILES
BrC1=C(NC2=NCCN2)C=CC2=C1N=CC=N2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Quinoxalines
Substructures
  • Imidazolines
  • Benzene and Derivatives
  • Aryl Halides
  • Pyrazines
  • Imidazoles
  • Heterocyclic compounds
  • Guanidines
  • Aromatic compounds
  • Carboxamidines
  • Anilines
  • Quinoxalines
  • Halobenzenes
Pharmacology
Indication For the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
Pharmacodynamics Brimonidine significantly lowers intraocular pressure with minimal effects on cardiovascular and pulmonary parameters. It lowers intraocular pressure by reducing aqueous humor production and increasing uveoscleral outflow.
Mechanism of action Brimonidine is an alpha adrenergic receptor agonist (primarily alpha-2). It has a peak ocular hypotensive effect occurring at two hours post-dosing. Fluorophotometric studies in animals and humans suggest that Brimonidine has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow.
Absorption Minimal systemic absorption occurs after ocular insertion.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Metabolized primarily by the liver.

Enzyme Metabolite Reaction Km Vmax
Aldehyde oxidase 2-oxobrimonidine Oxidation
Aldehyde oxidase 3-oxobrimonidine Oxidation
Route of elimination It is metabolized primarily by the liver. Urinary excretion is the major route of elimination of the drug and its metabolites.
Half life 2 hours
Clearance Not Available
Toxicity Oral LD50 is 50 mg/kg in mice and 100 mg/kg in rats.
Affected organisms
  • Humans and other mammals
Pathways Not Available
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
Dosage forms
Form Route Strength
Liquid Ophthalmic
Solution Ophthalmic
Prices
Unit description Cost Unit
Alphagan P 15ml Bottle .15% 15ml Bottle 228.5 USD bottle
Brimonidine Tartrate 0.15% Solution 15ml Bottle 218.5 USD bottle
Alphagan P 0.1% Solution 15ml Bottle 208.94 USD bottle
Alphagan P 10ml Bottle .15% 10ml Bottle 152.32 USD bottle
Brimonidine Tartrate 0.15% Solution 10ml Bottle 145.65 USD bottle
Alphagan P 0.1% Solution 10ml Bottle 143.97 USD bottle
Alphagan P 5ml Bottle .15% 5ml Bottle 79.52 USD bottle
Brimonidine Tartrate 0.15% Solution 5ml Bottle 72.85 USD bottle
Brimonidine Tartrate 0.2% Solution 10ml Bottle 67.85 USD bottle
Brimonidine Tartrate 0.2% Solution 15ml Bottle 56.88 USD bottle
Brimonidine Tartrate 0.2% Solution 5ml Bottle 33.96 USD bottle
Brimonidine tartrate 0.15% drp 29.82 USD ml
Alphagan p 0.15% eye drops 14.65 USD ml
Alphagan p 0.1% drops 13.85 USD ml
Brimonidine 0.2% eye drop 6.53 USD ml
Alphagan 0.2 % Solution 3.72 USD ml
Apo-Brimonidine 0.2 % Solution 2.08 USD ml
Pms-Brimonidine 0.2 % Solution 2.08 USD ml
Ratio-Brimonidine 0.2 % Solution 2.08 USD ml
Sandoz Brimonidine 0.2 % Solution 2.08 USD ml
Patents
Country Patent Number Approved Expires
United States 7265117 2005-08-19 2025-08-19
United States 5424078 1995-06-13 2012-06-13
Canada 2173974 2006-05-02 2014-09-19
Canada 2225626 2002-09-03 2016-06-17
Properties
State solid
Melting point 207.5 oC
Experimental Properties
Property Value Source
water solubility Soluble (1.5 mg/mL) PhysProp
logP 1.7 PhysProp
Predicted Properties
Property Value Source
water solubility 1.54e-01 g/l ALOGPS
logP 1.27 ALOGPS
logP 1.37 ChemAxon Molconvert
logS -3.28 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 62.20 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 68.49 ChemAxon Molconvert
polarizability 25.74 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02076 Link_out
KEGG Compound C07886 Link_out
PubChem Compound 2435 Link_out
PubChem Substance 46507305 Link_out
ChemSpider 2341 Link_out
ChEBI 3175 Link_out
ChEMBL 3175 Link_out
Therapeutic Targets Database DAP000280 Link_out
PharmGKB PA448665 Link_out
Drug Product Database 2243026 Link_out
RxList http://www.rxlist.com/cgi/generic3/alphagan-p.htm Link_out
Drugs.com http://www.drugs.com/cdi/brimonidine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Brimonidine Link_out
ATC Codes
  • S01EA05
AHFS Codes
  • 52:92.00
PDB Entries Not Available
FDA label show (517.1 KB)
MSDS show (20.9 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Alpha-2A adrenergic receptor

Pharmacological action: yes
Actions: agonist

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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Organism class: human
UniProt ID: P08913 Link_out
Gene: ADRA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Alpha-2B adrenergic receptor

Pharmacological action: yes
Actions: agonist

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 > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol

Organism class: human
UniProt ID: P18089 Link_out
Gene: ADRA2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

3. Alpha-2C adrenergic receptor

Pharmacological action: yes
Actions: agonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins

Organism class: human
UniProt ID: P18825 Link_out
Gene: ADRA2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
Enzymes

1. Aldehyde oxidase

Actions: substrate

An aldehyde + H(2)O + O(2) = a carboxylic acid + H(2)O(2)

UniProt ID: Q06278 Link_out
Gene: AOX1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on August 03, 2011 15:18

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.