Identification

Name
Naphazoline
Accession Number
DB06711
Type
Small Molecule
Groups
Approved, Investigational
Description

Naphazoline is a rapid acting sympathomimetic vasoconstrictor of occular artierioles. It acts to decrease congestion of the conjunctiva and is found in many over-the-counter eye drops.

Structure
Thumb
Synonyms
  • Nafazolin
Product Ingredients
IngredientUNIICASInChI Key
Naphazoline hydrochlorideMZ1131787D550-99-2DJDFFEBSKJCGHC-UHFFFAOYSA-N
Naphazoline nitrateSC99GR1T5S5144-52-5ZAHXYMFVNNUHCP-UHFFFAOYSA-N
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AK-ConSolution / drops1 mg/1mLOphthalmicPhysicians Total Care, Inc.2000-07-282012-06-30Us
AK-ConSolution / drops1 mg/1mLOphthalmicPreferreed Pharmaceuticals Inc.2005-03-242018-01-23Us
AK-ConSolution1 mg/1mLOphthalmicRebel Distributors1974-08-22Not applicableUs
AlbalonSolution1 mg/1mLOphthalmicAllergan Inc.1984-11-012008-10-21Us
NaphazolineSolution / drops1 mg/1mLOphthalmicAkorn1995-12-192017-09-30Us
NaphazolineSolution / drops1 mg/1mLOphthalmicPreferreed Pharmaceuticals Inc.2013-04-22Not applicableUs
NaphazolineSolution / drops1 mg/1mLOphthalmicA S Medication Solutions1995-12-19Not applicableUs
NaphazolineSolution / drops1 mg/1mLOphthalmicA-S Medication Solutions1995-12-192017-09-30Us
NaphazolineSolution / drops1 mg/1mLOphthalmicProficient Rx LP1995-12-19Not applicableUs
Naphazoline HydrochlorideSolution / drops1 mg/1mLOphthalmicPhysicians Total Care, Inc.1994-05-252009-06-30Us
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AlbalonSolution / drops.1 %OphthalmicAllergan1970-12-31Not applicableCanada
Clear EyesLiquid.012 %OphthalmicPrestige Brands Inc2004-03-24Not applicableCanada
Clear Eyes By Murine Eye DpsLiquid.012 %OphthalmicAbbott1970-12-312003-10-10Canada
Diopticon Liq 0.1%Solution0.1 %OphthalmicEberth Pharmaceuticals Inc1994-12-31Not applicableCanada
Naphcon ForteSolution0.1 %OphthalmicAlcon, Inc.1977-12-31Not applicableCanada
NazalLiquid50 mg/100mLNasalSato Pharmaceutical1990-06-11Not applicableUs
Nazil OftenoSolution / drops0.2 mg/1mLOphthalmicLABORATORIOS SOPHIA, S.A. DE C.V.2010-04-122015-04-29Us
Odan-naphazolineSolution.1 %OphthalmicOdan Laboratories Ltd1986-12-31Not applicableCanada
Opcon Oph Soln 0.1%Solution / drops.1 %OphthalmicBausch & Lomb Inc1987-12-311996-09-09Canada
Opti-tears Red EyeSolution0.1 %OphthalmicAlcon, Inc.2017-04-04Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
7 Select Redness ReliefNaphazoline hydrochloride (0.00012 mg/1mL) + Glycerin (0.0025 mg/1mL)Solution / dropsOphthalmic7-Select, Inc2017-03-28Not applicableUs
Advanced Eye Relief/ Redness Instant ReliefNaphazoline hydrochloride (0.1 mg/1mL) + Polyethylene glycol 300 (2 mg/1mL)Solution / dropsOphthalmicBauch & Lomb Incorporated2010-09-13Not applicableUs
Advanced Eye Relief/ Redness Maximum ReliefNaphazoline hydrochloride (0.3 mg/1mL) + Hypromellose (5 mg/1mL)Solution / dropsOphthalmicPreferreed Pharmaceuticals Inc.2010-09-02Not applicableUs
Advanced Eye Relief/ Redness Maximum ReliefNaphazoline hydrochloride (0.3 mg/1mL) + Hypromellose (5 mg/1mL)Solution / dropsOphthalmicBauch & Lomb Incorporated2010-09-02Not applicableUs
Albalon ANaphazoline hydrochloride (.05 %) + Antazoline phosphate (.5 %)LiquidOphthalmicAllergan1978-12-31Not applicableCanada
Allergy Eye DropsNaphazoline hydrochloride (0.25 mg/1mL) + Pheniramine maleate (3 mg/1mL)Solution / dropsOphthalmicCVS Health2013-01-25Not applicableUs
Allergy Eye DropsNaphazoline hydrochloride (0.02675 %) + Pheniramine maleate (0.315 %)Solution / dropsOphthalmicBausch & Lomb Inc2013-02-27Not applicableCanada
Allergy Eye DropsNaphazoline hydrochloride (0.25 mg/1mL) + Pheniramine maleate (3 mg/1mL)Solution / dropsOphthalmicChain Drug Consortium2014-01-10Not applicableUs
Blue CollyriumNaphazoline hydrochloride (0.5 mg) + Methylene blue (0.2 mg)LiquidOphthalmicSandoz Canada Incorporated1997-05-13Not applicableCanada
CareOne Maximum Strength Redness ReliefNaphazoline hydrochloride (0.00015 mg/1mL) + Glycerin (0.0025 mg/1mL)Solution / dropsOphthalmicFoodhold U.S.A.2017-05-18Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
NaphconNaphazoline hydrochloride (1 mg/1mL)SolutionOphthalmicAlcon2006-04-20Not applicableUs
VasoconNaphazoline hydrochloride (1 mg/1mL)SolutionOphthalmicCiba Vision2006-08-31Not applicableUs
Categories
UNII
H231GF11BV
CAS number
835-31-4
Weight
Average: 210.2744
Monoisotopic: 210.115698458
Chemical Formula
C14H14N2
InChI Key
CNIIGCLFLJGOGP-UHFFFAOYSA-N
InChI
InChI=1S/C14H14N2/c1-2-7-13-11(4-1)5-3-6-12(13)10-14-15-8-9-16-14/h1-7H,8-10H2,(H,15,16)
IUPAC Name
2-(naphthalen-1-ylmethyl)-4,5-dihydro-1H-imidazole
SMILES
C(C1=NCCN1)C1=CC=CC2=CC=CC=C12

Pharmacology

Indication

Naphazoline is primarily indicated in conditions like Corneal vascularity, Hyperaemia, Itching, Nasal congestion, and can also be given in adjunctive therapy as an alternative drug of choice in Sinusitis

Associated Conditions
Associated Therapies
Pharmacodynamics

Naphazoline is a direct acting sympathomimetic adrenergic alpha-agonist used to induce systemic vasoconstriction, thereby decreasing nasal congestion and inducing constriction around the conjunctiva. The sympathomimetic action of Naphazoline constricts the smaller arterioles of the nasal passages, producing a decongesting effect. Naphazoline ophthalmic causes constriction of blood vessels in the eyes. It also decreases itching and irritation of the eyes. aphazoline constricts the vascular system of the conjunctiva. It is presumed that this effect is due to direct stimulation action of the drug upon the alpha adrenergic receptors in the arterioles of the conjunctiva resulting in decreased conjunctival congestion. Naphazoline belongs to the imidazoline class of sympathomimetics.

Mechanism of action

Naphazoline is a direct acting sympathomimetic drug, which acts on alpha-adrenergic receptors in the arterioles of the nasal mucosa. This activates the adrenal system to yield systemic vasoconstrction. In producing vasoconstriction, the result is a decrease in blood flow in the nasal passages and consequently decreased nasal congestion. The vasoconstriction means that there is less pressure in the capillaries and less water can filter out, thus less discharge is made.

TargetActionsOrganism
AAlpha-1A adrenergic receptor
agonist
Human
AAlpha-2A adrenergic receptor
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Extended usage of Naphazoline can result in decreased effectiveness or a build up of tolerance against the drug. The number of receptors decreases, and when the administration of the drug is ceased, chronic congestion can occur; this is called rhinitis medicamentosa, commonly referred to as rebound congestion. Moreover long-term overdosing can cause degenerative changes in nasal mucous membranes that pose another health problem.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcebutololThe therapeutic efficacy of Naphazoline can be decreased when used in combination with Acebutolol.
AcepromazineThe therapeutic efficacy of Naphazoline can be decreased when used in combination with Acepromazine.
AlfuzosinThe therapeutic efficacy of Naphazoline can be decreased when used in combination with Alfuzosin.
AlprenololThe therapeutic efficacy of Naphazoline can be decreased when used in combination with Alprenolol.
AmineptineAmineptine may increase the vasopressor activities of Naphazoline.
AmitriptylineAmitriptyline may increase the vasopressor activities of Naphazoline.
AmitriptylinoxideAmitriptylinoxide may increase the vasopressor activities of Naphazoline.
AmoxapineAmoxapine may increase the vasopressor activities of Naphazoline.
AnisodamineThe therapeutic efficacy of Naphazoline can be decreased when used in combination with Anisodamine.
AripiprazoleThe therapeutic efficacy of Naphazoline can be decreased when used in combination with Aripiprazole.
Food Interactions
Not Available

References

Synthesis Reference

Roy W. Bryant, Ravi Parihar, Thomas Rowe, Susan Caballa, "Methods of Making and Using Stable Pharmaceutical Compositions Comprising Ketotifen and Naphazoline." U.S. Patent US20110312998, issued December 22, 2011.

US20110312998
General References
Not Available
External Links
Human Metabolome Database
HMDB0015656
KEGG Drug
D08253
PubChem Compound
4436
PubChem Substance
99443263
ChemSpider
4283
BindingDB
50001922
ChEBI
93363
ChEMBL
CHEMBL761
PharmGKB
PA165958384
Wikipedia
Naphazoline
ATC Codes
R01AB02 — NaphazolineS01GA01 — NaphazolineR01AA08 — NaphazolineS01GA51 — Naphazoline, combinations
AHFS Codes
  • 52:32.00 — Vasoconstrictors

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentNeoplasms Malignant1
2RecruitingTreatmentMetastatic Castration-Resistant Prostate Cancer Patients1
2, 3RecruitingTreatmentProstate Cancer1
3CompletedTreatmentConjunctivitis, Seasonal Allergic2
3RecruitingTreatmentAcute Lymphoblastic Leukemia, Pediatric1
3RecruitingTreatmentNasal Stuffiness / Rhinitis1
4Not Yet RecruitingTreatmentMyopathies1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidOphthalmic.012 %
LiquidOphthalmic
Solution / dropsOphthalmic
Solution / dropsOphthalmic1 mg/1mL
LiquidNasal50 mg/100mL
Solution / dropsOphthalmic0.2 mg/1mL
SolutionOphthalmic.1 %
Solution / dropsOphthalmic.1 %
Solution / dropsOphthalmic1 mg/1
SprayNasal0.1 mL/20mL
Suspension / dropsNasal0.125 mL/25mL
LiquidOphthalmic.1 %
SolutionOphthalmic
SolutionOphthalmic0.1 %
LiquidNasal
Solution / dropsOphthalmic12 mg/100mL
Solution / dropsOphthalmic0.012 %
SolutionOphthalmic1 mg/1mL
Solution / dropsOphthalmic1 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0381 mg/mLALOGPS
logP3.44ALOGPS
logP2.19ChemAxon
logS-3.7ALOGPS
pKa (Strongest Basic)10.19ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area24.39 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity65.52 m3·mol-1ChemAxon
Polarizability23.77 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9936
Blood Brain Barrier+0.9693
Caco-2 permeable-0.6307
P-glycoprotein substrateSubstrate0.7448
P-glycoprotein inhibitor INon-inhibitor0.8385
P-glycoprotein inhibitor IINon-inhibitor0.6449
Renal organic cation transporterInhibitor0.8506
CYP450 2C9 substrateNon-substrate0.8202
CYP450 2D6 substrateSubstrate0.7094
CYP450 3A4 substrateNon-substrate0.7297
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.92
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9479
CYP450 3A4 inhibitorNon-inhibitor0.9206
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.889
Ames testNon AMES toxic0.8156
CarcinogenicityNon-carcinogens0.9476
BiodegradationNot ready biodegradable0.9961
Rat acute toxicity2.6904 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7043
hERG inhibition (predictor II)Non-inhibitor0.5354
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/MSsplash10-03di-0390000000-bf587920984867425a82

Taxonomy

Description
This compound belongs to the class of organic compounds known as naphthalenes. These are compounds containing a naphthalene moiety, which consists of two fused benzene rings.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Naphthalenes
Sub Class
Not Available
Direct Parent
Naphthalenes
Alternative Parents
Imidolactams / Imidazolines / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Carboxamidines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Naphthalene / Imidolactam / 2-imidazoline / Azacycle / Organoheterocyclic compound / Organic 1,3-dipolar compound / Propargyl-type 1,3-dipolar organic compound / Carboximidamide / Carboxylic acid amidine / Amidine
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

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) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Bogacka E: [Decongestants in treatment of nasal obstruction]. Otolaryngol Pol. 1999;53(3):347-52. [PubMed:10481510]
  2. Leonardi A: Emerging drugs for ocular allergy. Expert Opin Emerg Drugs. 2005 Aug;10(3):505-20. [PubMed:16083326]
  3. Piletz JE, Zhu H, Chikkala DN: Comparison of ligand binding affinities at human I1-imidazoline binding sites and the high affinity state of alpha-2 adrenoceptor subtypes. J Pharmacol Exp Ther. 1996 Nov;279(2):694-702. [PubMed:8930173]
  4. Hrometz SL, Edelmann SE, McCune DF, Olges JR, Hadley RW, Perez DM, Piascik MT: Expression of multiple alpha1-adrenoceptors on vascular smooth muscle: correlation with the regulation of contraction. J Pharmacol Exp Ther. 1999 Jul;290(1):452-63. [PubMed:10381812]
  5. Kai T: [Effects of topical alpha 1- and beta 2-adrenoceptor stimulants on nasal nitric oxide level]. Nihon Jibiinkoka Gakkai Kaiho. 1999 Jul;102(7):898-906. [PubMed:10459292]
  6. Ogidigben MJ, Chu TC, Potter DE: Naphazoline-induced suppression of aqueous humor pressure and flow: involvement of central and peripheral alpha(2)/I(1) receptors. Exp Eye Res. 2001 Mar;72(3):331-9. [PubMed:11180982]
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 oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Piletz JE, Zhu H, Chikkala DN: Comparison of ligand binding affinities at human I1-imidazoline binding sites and the high affinity state of alpha-2 adrenoceptor subtypes. J Pharmacol Exp Ther. 1996 Nov;279(2):694-702. [PubMed:8930173]
  2. Fukushima H, Norimoto K, Seki T, Nishiguchi T, Nakamura T, Konobu T, Nishio K, Okuchi K: Acute pulmonary edema associated with naphazoline ingestion. Clin Toxicol (Phila). 2008 Mar;46(3):254-6. [PubMed:17852165]
  3. Ogidigben MJ, Chu TC, Potter DE: Naphazoline-induced suppression of aqueous humor pressure and flow: involvement of central and peripheral alpha(2)/I(1) receptors. Exp Eye Res. 2001 Mar;72(3):331-9. [PubMed:11180982]

Drug created on May 16, 2010 11:05 / Updated on September 21, 2018 20:42