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Identification
NameApraclonidine
Accession NumberDB00964  (APRD00012)
TypeSmall Molecule
GroupsApproved
Description

Apraclonidine, also known as iopidine, is a sympathomimetic used in glaucoma therapy. It is an alpha2-adrenergic agonist.

Structure
Thumb
Synonyms
4-Aminoclonidine
Apraclonidina
Apraclonidinum
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apraclonidinesolution5.75 mg/mLophthalmicFalcon Pharmaceuticals, Ltd.2009-07-192016-04-05Us
Iopidinesolution5 mg/mLophthalmicAlcon Laboratories, Inc.1993-10-012016-04-23Us
Iopidinesolution/ drops10 mg/mLophthalmicAlcon Laboratories, Inc.1988-05-152016-04-23Us
Iopidine Liq Oph 0.5%liquid.5 %ophthalmicAlcon Canada Inc1995-12-31Not applicableCanada
Iopidine Oph Sol 1%liquid1 %ophthalmicAlcon Canada Inc1992-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apraclonidine Ophthalmicsolution/ drops5 mg/mLophthalmicAkorn Inc.2009-08-122016-04-05Us
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Apraclonidine Hydrochloride
Thumb
  • InChI Key: OTQYGBJVDRBCHC-UHFFFAOYSA-N
  • Monoisotopic Mass: 280.004929493
  • Average Mass: 281.569
DBSALT000819
Categories
UNII843CEN85DI
CAS number66711-21-5
WeightAverage: 245.109
Monoisotopic: 244.028251754
Chemical FormulaC9H10Cl2N4
InChI KeyInChIKey=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)
IUPAC Name
2,6-dichloro-N1-(4,5-dihydro-1H-imidazol-2-yl)benzene-1,4-diamine
SMILES
NC1=CC(Cl)=C(NC2=NCCN2)C(Cl)=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as substituted anilines. These are organic compound containing an aniline group substituted at one or more positions.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassAnilines
Direct ParentSubstituted anilines
Alternative Parents
Substituents
  • Substituted aniline
  • 1,3-dichlorobenzene
  • Halobenzene
  • Chlorobenzene
  • Primary aromatic amine
  • Aryl halide
  • Aryl chloride
  • 2-imidazoline
  • Guanidine
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Hydrocarbon derivative
  • Primary amine
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsApraclonidine 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 actionApraclonidine 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.
Related Articles
AbsorptionTopical 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 distributionNot Available
Protein binding98.7%
MetabolismNot Available
Route of eliminationNot Available
Half life8 hours
ClearanceNot Available
ToxicityAccidental 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9685
Blood Brain Barrier+0.9398
Caco-2 permeable+0.8503
P-glycoprotein substrateSubstrate0.625
P-glycoprotein inhibitor INon-inhibitor0.9406
P-glycoprotein inhibitor IINon-inhibitor0.9142
Renal organic cation transporterInhibitor0.7327
CYP450 2C9 substrateNon-substrate0.8621
CYP450 2D6 substrateNon-substrate0.7005
CYP450 3A4 substrateNon-substrate0.6636
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.7046
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8713
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8947
Ames testNon AMES toxic0.8937
CarcinogenicityNon-carcinogens0.9263
BiodegradationNot ready biodegradable0.9954
Rat acute toxicity3.4656 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8192
hERG inhibition (predictor II)Non-inhibitor0.891
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Akorn inc
  • Alcon laboratories inc
Packagers
Dosage forms
FormRouteStrength
Solutionophthalmic5.75 mg/mL
Solution/ dropsophthalmic5 mg/mL
Solutionophthalmic5 mg/mL
Solution/ dropsophthalmic10 mg/mL
Liquidophthalmic.5 %
Liquidophthalmic1 %
Prices
Unit descriptionCostUnit
Iopidine 0.5% Solution 10ml Bottle196.37USD bottle
Iopidine 0.5% Solution 5ml Bottle98.84USD bottle
Iopidine 1 Box = 24 Packets Plastic Container16.44USD plastic
Iopidine 1% eye drops15.81USD each
Iopidine 0.5 % Solution4.79USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5212196 No1993-05-182010-05-18Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.409 mg/mLALOGPS
logP2.14ALOGPS
logP1.66ChemAxon
logS-2.8ALOGPS
pKa (Strongest Basic)8.48ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area62.44 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity63.79 m3·mol-1ChemAxon
Polarizability23.27 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  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:16808679 ]
  2. Aslanides lM, Tsiklis NS, Ozkilic E, Coskunseven E, Pallikaris lG, 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:16805122 ]
  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:16518162 ]
  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:16418668 ]
  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:16355950 ]
  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:14575724 ]
External Links
ATC CodesS01EA03
AHFS Codes
  • 52:92.00
PDB EntriesNot Available
FDA labelDownload (119 KB)
MSDSDownload (57.1 KB)
Interactions
Drug Interactions
Drug
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Apraclonidine.
AmitriptylineThe therapeutic efficacy of Apraclonidine can be decreased when used in combination with Amitriptyline.
ButabarbitalButabarbital may increase the hypotensive activities of Apraclonidine.
ButethalButethal may increase the hypotensive activities of Apraclonidine.
DuloxetineApraclonidine may increase the orthostatic hypotensive activities of Duloxetine.
HeptabarbitalHeptabarbital may increase the hypotensive activities of Apraclonidine.
HexobarbitalHexobarbital may increase the hypotensive activities of Apraclonidine.
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Apraclonidine.
LevodopaApraclonidine may increase the orthostatic hypotensive activities of Levodopa.
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Apraclonidine.
MethohexitalMethohexital may increase the hypotensive activities of Apraclonidine.
MianserinThe therapeutic efficacy of Apraclonidine can be decreased when used in combination with Mianserin.
MirtazapineMirtazapine may decrease the antihypertensive activities of Apraclonidine.
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Apraclonidine.
NicorandilNicorandil may increase the hypotensive activities of Apraclonidine.
PentobarbitalPentobarbital may increase the hypotensive activities of Apraclonidine.
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Apraclonidine.
PrimidonePrimidone may increase the hypotensive activities of Apraclonidine.
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Apraclonidine.
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Apraclonidine.
RisperidoneApraclonidine may increase the hypotensive activities of Risperidone.
SecobarbitalSecobarbital may increase the hypotensive activities of Apraclonidine.
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Apraclonidine.
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Tedizolid Phosphate is combined with Apraclonidine.
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Apraclonidine.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Apraclonidine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianser...
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
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:17139284 ]
  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:17016423 ]
  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:11481271 ]
  4. Moodley AA, Spooner RB: Apraclonidine in the diagnosis of Horner's syndrome. S Afr Med J. 2007 Jul;97(7):506-7. [PubMed:17824139 ]
  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:16921219 ]
  6. Authors unspecified: New topical drugs for open-angle glaucoma. Drug Ther Bull. 2003 Feb;41(2):12-4. [PubMed:12630335 ]
  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:14575724 ]
  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:15748550 ]
  9. Sueke H, Chandna A: Using apraclonidine in diagnosing Horner syndrome in children. Am J Ophthalmol. 2010 May;149(5):869; author reply 870. doi: 10.1016/j.ajo.2010.01.023. [PubMed:20399934 ]
  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:17572343 ]
  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:16935593 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Protein heterodimerization activity
Specific Function:
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. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
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:17824139 ]
  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:16921219 ]
  3. Sueke H, Chandna A: Using apraclonidine in diagnosing Horner syndrome in children. Am J Ophthalmol. 2010 May;149(5):869; author reply 870. doi: 10.1016/j.ajo.2010.01.023. [PubMed:20399934 ]
  4. Kawasaki A, Borruat FX: False negative apraclonidine test in two patients with Horner syndrome. Klin Monbl Augenheilkd. 2008 May;225(5):520-2. doi: 10.1055/s-2008-1027349. [PubMed:18454417 ]
  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:17572343 ]
  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:16935593 ]
  7. Freedman KA, Brown SM: Topical apraclonidine in the diagnosis of suspected Horner syndrome. J Neuroophthalmol. 2005 Jun;25(2):83-5. [PubMed:15937427 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phent...
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
References
  1. Liu JH, Dacus AC, Bartels SP: Adrenergic mechanism in circadian elevation of intraocular pressure in rabbits. Invest Ophthalmol Vis Sci. 1991 Jul;32(8):2178-83. [PubMed:1676991 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12