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Identification
Name Apraclonidine
Accession Number DB00964 (APRD00012)
Type small molecule
Groups approved
Description

Apraclonidine, also known as iopidine, is a sympathomimetic used in glaucoma therapy. It is an alpha2-adrenergic agonist.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Apraclonidina [INN-Spanish]
Apraclonidine Hydrochloride
Apraclonidinum [INN-Latin]
P-Aminoclonidine Hydrochloride
Salts Not Available
Brand names
Name Company
Aplonidine
Iopidine
Iopidine Eye
Brand mixtures Not Available
Categories
  • EENT Drugs
  • Adrenergic alpha-Agonists
  • Antiglaucomic Agents
  • Ophthalmics
CAS number 66711-21-5
Weight Average: 245.109
Monoisotopic: 244.028251754
Chemical Formula C9H10Cl2N4
InChI Key InChIKey=IEJXVRYNEISIKR-UHFFFAOYSA-N
InChI
InChI=1S/C9H10Cl2N4/c10-6-3-5(12)4-7(11)8(6)15-9-13-1-2-14-9/h3-4H,1-2,12H2,(H2,13,14,15)
Plain Text
IUPAC Name
2,6-dichloro-1-N-(4,5-dihydro-1H-imidazol-2-yl)benzene-1,4-diamine
SMILES
NC1=CC(Cl)=C(NC2=NCCN2)C(Cl)=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzene and Derivatives
  • Halobenzenes
  • Anilines
Substructures
  • Imidazolines
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Imidazoles
  • Heterocyclic compounds
  • Guanidines
  • Aromatic compounds
  • Carboxamidines
  • Anilines
Pharmacology
Indication For prevention or reduction of intraoperative and postoperative increases in intraocular pressure (IOP) before and after ocular laser surgery when used prophylactically. Also used as a short-term adjunctive therapy in patients with open-angle glaucoma who are on maximally tolerated medical therapy requiring additional IOP reduction.
Pharmacodynamics Apraclonidine 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 Apraclonidine is a relatively selective alpha2 adrenergic receptor agonist that stimulates alpha1 receptors to a lesser extent. It has a peak ocular hypotensive effect occurring at two hours post-dosing. The exact mechanism of action is unknown, but fluorophotometric studies in animals and humans suggest that Apraclonidine has a dual mechanism of action by reducing aqueous humor production through the constriction of afferent ciliary process vessels, and increasing uveoscleral outflow.
Absorption Topical use of apraclonidine ophthalmic solution leads to systemic absorption. Studies of apraclonidine (0.5% ophthalmic solution) dosed one drop three times a day in both eyes for 10 days in normal volunteers yielded mean peak and trough concentrations of 0.9 ng/mL and 0.5 ng/mL, respectively.
Volume of distribution Not Available
Protein binding 98.7%
Metabolism
Not Available
Route of elimination Not Available
Half life 8 hours
Clearance Not Available
Toxicity Accidental or intentional ingestion of oral apraclonidine has been reported to cause apnea, arrhythmias, asthenia, bradycardia, conduction defects, diminished or absent reflexes, dryness of the mouth, hypotension, hypothermia, hypoventilation, irritability, lethargy, miosis, pallor, respiratory depression, sedation or coma, seizure, somnolence, transient hypertension, and vomiting.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Akorn inc
  • Alcon laboratories inc
Packagers
Dosage forms
Form Route Strength
Liquid Ophthalmic
Solution / drops Ophthalmic
Prices
Unit description Cost Unit
Iopidine 0.5% Solution 10ml Bottle 196.37 USD bottle
Iopidine 0.5% Solution 5ml Bottle 98.84 USD bottle
Iopidine 1 Box = 24 Packets Plastic Container 16.44 USD plastic
Iopidine 1% eye drops 15.81 USD each
Iopidine 0.5 % Solution 4.79 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 5212196 1993-05-18 2010-05-18
Properties
State solid
Experimental Properties
Property Value Source
logP 1.4 Not Available
Predicted Properties
Property Value Source
water solubility 4.09e-01 g/l ALOGPS
logP 2.14 ALOGPS
logP 1.66 ChemAxon
logS -2.8 ALOGPS
pKa (strongest basic) 8.48 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 62.44 ChemAxon
rotatable bond count 1 ChemAxon
refractivity 63.79 ChemAxon
polarizability 23.27 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Chen PL, Chen JT, Lu DW, Chen YC, Hsiao CH: Comparing efficacies of 0.5% apraclonidine with 4% cocaine in the diagnosis of horner syndrome in pediatric patients. J Ocul Pharmacol Ther. 2006 Jun;22(3):182-7. Pubmed
  2. Aslanides M, Tsiklis NS, Ozkilic E, Coskunseven E, Pallikaris G, Jankov MR: The effect of topical apraclonidine on subconjunctival hemorrhage and flap adherence in LASIK patients. J Refract Surg. 2006 Jun;22(6):585-8. Pubmed
  3. Koc F, Kansu T, Kavuncu S, Firat E: Topical apraclonidine testing discloses pupillary sympathetic denervation in diabetic patients. J Neuroophthalmol. 2006 Mar;26(1):25-9. Pubmed
  4. Garibaldi DC, Hindman HB, Grant MP, Iliff NT, Merbs SL: Effect of 0.5% apraclonidine on ptosis in Horner syndrome. Ophthal Plast Reconstr Surg. 2006 Jan-Feb;22(1):53-5. Pubmed
  5. Onal S, Gozum N, Gucukoglu A: Effect of apraclonidine versus dorzolamide on intraocular pressure after phacoemulsification. Ophthalmic Surg Lasers Imaging. 2005 Nov-Dec;36(6):457-62. Pubmed
  6. Costa VP, Harris A, Stefansson E, Flammer J, Krieglstein GK, Orzalesi N, Heijl A, Renard JP, Serra LM: The effects of antiglaucoma and systemic medications on ocular blood flow. Prog Retin Eye Res. 2003 Nov;22(6):769-805. Pubmed
External Links
Resource Link
KEGG Compound C07668 Link_out
PubChem Compound 2216 Link_out
PubChem Substance 46505614 Link_out
ChemSpider 2130 Link_out
BindingDB 50021812 Link_out
ChEBI 2788 Link_out
ChEMBL 2788 Link_out
Therapeutic Targets Database DAP000236 Link_out
PharmGKB PA164748866 Link_out
Drug Product Database 2076306 Link_out
RxList http://www.rxlist.com/cgi/generic2/apraclonidine.htm Link_out
Drugs.com http://www.drugs.com/cdi/apraclonidine-drops.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Apraclonidine Link_out
ATC Codes
  • S01EA03
AHFS Codes
  • 52:92.00
PDB Entries Not Available
FDA label show (119 KB)
MSDS show (57.1 KB)
Interactions
Drug Interactions
Drug Interaction
Tranylcypromine The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the alpha2-agonist, Apraclonidine. Concomitant therapy is contraindicated.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. 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
  4. Moodley AA, Spooner RB: Apraclonidine in the diagnosis of Horner’s syndrome. S Afr Med J. 2007 Jul;97(7):506-7. Pubmed
  5. Mirzai H, Baser EF: Congenital Horner’s syndrome and the usefulness of the apraclonidine test in its diagnosis. Indian J Ophthalmol. 2006 Sep;54(3):197-9. Pubmed
  6. New topical drugs for open-angle glaucoma. Drug Ther Bull. 2003 Feb;41(2):12-4. Pubmed
  7. Costa VP, Harris A, Stefansson E, Flammer J, Krieglstein GK, Orzalesi N, Heijl A, Renard JP, Serra LM: The effects of antiglaucoma and systemic medications on ocular blood flow. Prog Retin Eye Res. 2003 Nov;22(6):769-805. Pubmed
  8. Scheinfeld N: The use of apraclonidine eyedrops to treat ptosis after the administration of botulinum toxin to the upper face. Dermatol Online J. 2005 Mar 1;11(1):9. Pubmed
  9. Sueke H, Chandna A: Using apraclonidine in diagnosing Horner syndrome in children. Am J Ophthalmol. 2010 May;149(5):869; author reply 870. Pubmed
  10. Watts P, Satterfield D, Lim MK: Adverse effects of apraclonidine used in the diagnosis of Horner syndrome in infants. J AAPOS. 2007 Jun;11(3):282-3. Pubmed
  11. Chen PL, Hsiao CH, Chen JT, Lu DW, Chen WY: Efficacy of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients under low or high illumination. Am J Ophthalmol. 2006 Sep;142(3):469-74. Pubmed

2. Alpha-1A adrenergic receptor

Pharmacological action: yes
Actions: agonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Moodley AA, Spooner RB: Apraclonidine in the diagnosis of Horner’s syndrome. S Afr Med J. 2007 Jul;97(7):506-7. Pubmed
  2. Mirzai H, Baser EF: Congenital Horner’s syndrome and the usefulness of the apraclonidine test in its diagnosis. Indian J Ophthalmol. 2006 Sep;54(3):197-9. Pubmed
  3. Sueke H, Chandna A: Using apraclonidine in diagnosing Horner syndrome in children. Am J Ophthalmol. 2010 May;149(5):869; author reply 870. Pubmed
  4. Kawasaki A, Borruat FX: False negative apraclonidine test in two patients with Horner syndrome. Klin Monbl Augenheilkd. 2008 May;225(5):520-2. Pubmed
  5. Watts P, Satterfield D, Lim MK: Adverse effects of apraclonidine used in the diagnosis of Horner syndrome in infants. J AAPOS. 2007 Jun;11(3):282-3. Pubmed
  6. Chen PL, Hsiao CH, Chen JT, Lu DW, Chen WY: Efficacy of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients under low or high illumination. Am J Ophthalmol. 2006 Sep;142(3):469-74. Pubmed
  7. Freedman KA, Brown SM: Topical apraclonidine in the diagnosis of suspected Horner syndrome. J Neuroophthalmol. 2005 Jun;25(2):83-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19