APRACLONIDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H10Cl2N4
Molecular Weight	245.109
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=CC(Cl)=C(NC2=NCCN2)C(Cl)=C1

InChI

InChIKey=IEJXVRYNEISIKR-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/19779s018,019lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/ppa/apraclonidine.html | https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dc7d3a9f-c0b9-411c-9c62-0a14f1718b00

Apraclonidine (IOPIDINE) is an α2-adrenergic receptor agonist and a weak α1-adrenergic receptor agonist. It is used for the prevention and treatment of postsurgical intraocular pressure elevation. The following adverse events, occurring in less than 2% of patients, were reported in association with the use of IOPIDINE Ophthalmic Solution in laser surgery: ocular injection, upper lid elevation, irregular heart rate, nasal decongestion, ocular inflammation, conjunctival blanching, and mydriasis. Interactions with other agents have not been investigated.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Alpha-2A adrenergic receptor 26 Target ID: P08913 Gene ID: 150.0 Gene Symbol: ADRA2A Target Organism: Homo sapiens (Human) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/19779s018,019lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/6246501 \| https://www.ncbi.nlm.nih.gov/pubmed/11481271	Agonist 2678
Adrenergic receptor alpha-1 169 Target ID: CHEMBL2094251 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/19779s018,019lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/6246501	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ocular hypertension 50 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/19779s018,019lbl.pdf	Preventing		Approved 8429	IOPIDINE Approved Use Apraclonidine hydrochloride ophthalmic solution) is indicated to control or prevent postsurgical elevations in intraocular pressure that occur in patients after argon laser trabeculplasty, argon laser iridotomy or Nd:YAG posterior capsulotomy. Launch Date 5.6782081E11

C_max

Value	Dose	Co-administered	Analyte	Population
0.9 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf	1 drop 3 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered:		APRACLONIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf	1 drop 3 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered:		APRACLONIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
74.5% DRUG LABEL https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiUl-C6ho7sAhWj_CoKHXPHBYkQFjAYegQIHBAB&url=http%3A%2F%2Fwww.ask.novartispharma.ca%2Fdownload.htm%3Fres%3Diopidine_scrip_e.pdf%26resTitleId%3D1430&usg=AOvVaw2NI2gLoHBJh4I8Nn1NkVE2	unknown, topical		APRACLONIDINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.5 % 2 times / day multiple, ophthalmic Recommended Dose: 0.5 %, 2 times / day Route: ophthalmic Route: multiple Dose: 0.5 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: intraocular pressure Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf	Disc. AE: Allergic reaction... AEs leading to discontinuation/dose reduction: Allergic reaction (12.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf

AEs

AE	Significance	Dose	Population
Allergic reaction	12.9% Disc. AE	0.5 % 2 times / day multiple, ophthalmic Recommended Dose: 0.5 %, 2 times / day Route: ophthalmic Route: multiple Dose: 0.5 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: intraocular pressure Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 270

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9305586/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2788	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2788
ZINC	ZINC000000020231	http://zinc15.docking.org/substances/ZINC000000020231

PubMed

Title	Date	PubMed
Apraclonidine and LASIK.	2005 Dec	16325717
Effect of apraclonidine versus dorzolamide on intraocular pressure after phacoemulsification.	2005 Nov-Dec	16355950
Brimonidine 0.15% versus apraclonidine 0.5% for prevention of intraocular pressure elevation after anterior segment laser surgery.	2005 Sep	16246772
Comparative efficacy of acetazolamide and apraclonidine in the control of intraocular pressure following phacoemulsification.	2006	17095879
Reduction of anterior-segment vascularity with preoperative topical apraclonidine 1%.	2006 Apr	16698500
Topical apraclonidine testing of pupillary sympathetic denervation in diabetic patients.	2006 Dec	17204928
Corneal thickness- and age-related biomechanical properties of the cornea measured with the ocular response analyzer.	2006 Dec	17122122
Effect of 0.5% apraclonidine on ptosis in Horner syndrome.	2006 Jan-Feb	16418668
Antagonism by imidazoline-type drugs of muscarinic and other receptors in the guinea-pig ileum.	2006 Jul	16879492
The management of glaucoma and intraocular hypertension: current approaches and recent advances.	2006 Jun	18360593
Comparing efficacies of 0.5% apraclonidine with 4% cocaine in the diagnosis of horner syndrome in pediatric patients.	2006 Jun	16808679
The effect of topical apraclonidine on subconjunctival hemorrhage and flap adherence in LASIK patients.	2006 Jun	16805122
Topical apraclonidine testing discloses pupillary sympathetic denervation in diabetic patients.	2006 Mar	16518162
Efficacy of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients under low or high illumination.	2006 Sep	16935593
Brinzolamide 1% versus apraclonidine 0.5% to prevent intraocular pressure elevation after neodymium:YAG laser posterior capsulotomy.	2006 Sep	16931262
Congenital Horner's syndrome and the usefulness of the apraclonidine test in its diagnosis.	2006 Sep	16921219
Genomic and functional conservation of sedative-hypnotic targets in the zebrafish.	2007 Apr	17496723
Apraclonidine in the diagnosis of Horner's syndrome.	2007 Jul	17824139
Adverse effects of apraclonidine used in the diagnosis of Horner syndrome in infants.	2007 Jun	17572343
Pharmacologic reversal of Horner's syndrome-related ptosis with apraclonidine.	2007 May	17580803
The acute morphologic changes that occur at the optic nerve head induced by medical reduction of intraocular pressure.	2007 Sep	17873718
Horner's syndrome, Pseudo-Horner's syndrome, and simple anisocoria.	2007 Sep	17764630
Congenital or acquired Horner's?	2007 Sep-Oct	17699962
The pupil.	2008 Feb	18180650
Medical management of primary open-angle glaucoma: Best practices associated with enhanced patient compliance and persistency.	2008 Feb 2	19920977
Use of 0.5% apraclonidine solution in evaluation of blepharoptosis.	2008 Jul-Aug	18645436
Post-penetrating keratoplasty glaucoma.	2008 Jul-Aug	18579984
The role of cyclosporine and mycophenolate in an orthotopic porcine-to-rat corneal xenotransplantation.	2008 Jun	18583888
Central alpha-2 adrenergic eye drops: case series of 3 pediatric systemic poisonings.	2008 Mar	18347496
Effects of central corneal thickness on the efficacy of topical ocular hypotensive medications.	2008 Mar	18344753
Differences in the histopathology and matrix metalloproteinase expression in Tenon's tissue of primary open-angle glaucoma and primary angle-closure glaucoma.	2008 Mar	18323704
Acupuncture treatment for idiopathic Horner's syndrome in a dog.	2008 Mar	18296897
False negative apraclonidine test in two patients with Horner syndrome.	2008 May	18454417
Recurrent serous macular detachment after topical ocular hypotensive medication.	2008 Nov	18537988
Fixed combination of topical brimonidine 0.2% and timolol 0.5% for glaucoma and uncontrolled intraocular pressure.	2008 Sep	19668752
Pupillary autonomic neuropathy simulating partial Horner syndrome in diabetes mellitus and its reversal with control of blood glucose.	2008 Sep	18769297
Positive apraclonidine test within two weeks of onset of Horner syndrome caused by carotid artery dissection.	2008 Sep	18769292
[Efficacy of topic ocular hipotensive agents after posterior capsulotomy].	2008 Sep-Oct	19039468
Topical apraclonidine to diagnose Bernard-Horner syndrome.	2009	19927485
Oral versus topical carbonic anhydrase inhibitors in ocular hypertension after scleral tunnel cataract surgery.	2009	19668590
Clinical efficacy and neuroprotective effects of brimonidine in the management of glaucoma and ocular hypertension.	2009	19668554
Brimonidine and apraclonidine as vasoconstrictors in adjustable strabismus surgery.	2009 Apr	19393510
Possible effect of systemic sympathicolytic drugs on apraclonidine test.	2009 Aug	19606173
[Unilateral allergic contact dermatitis of the eyelid caused by Iopimax].	2009 Dec	20038377
Nd: YAG capsulotomy for posterior capsule opacification after combined clear corneal phacoemulsification and vitrectomy.	2009 Feb	19436607
[Usefulness of apraclonidine in the diagnosis of Horner syndrome].	2009 Feb	19253181
False-negative apraclonidine testing in acute Horner syndrome.	2009 Feb	19169332
Exposure to topical apraclonidine in children with glaucoma.	2009 Jun-Jul	19525731
Ocular decompression retinopathy after trabeculectomy with mitomycin-C for angle recession glaucoma.	2009 Mar-Apr	19237794
Current pharmacologic testing for Horner syndrome.	2009 Sep	19664368

Patents

Sample Use Guides

In Vivo Use Guide

One drop of Ophthalmic Solution should be instilled in the scheduled operative eye one hour before initiating anterior segment laser surgery and a second drop should be instilled to the same eye immediately upon completion of the laser surgical procedure. Use a separate container for each single-drop dose and discard each container after use.

Route of Administration: Topical

In Vitro Use Guide

The alpha(2)-adrenoceptor agonists apraclonidine induced vasoconstriction in the porcine ciliary artery with the potency EC(50) equal to 13.0 nM.

Name

Type

Language

APRACLONIDINE

Official Name

English

APRACLONIDINE [VANDF]

Common Name

English

apraclonidine [INN]

Common Name

English

APRACLONIDINE [MI]

Common Name

English

Apraclonidine [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

S01EA03