Details of the Drug

General Information of Drug (ID: DMJFZDL)

• Drug Name: Naphazoline
• Synonyms: Antan; Clearine; Nafazolin; Nafazolina; Nafazoline; Naphazolinum; Naphthizine; Opcon; Nafazolina [DCIT]; Nafazoline [Spanish]; Naphazoline Monohydrochloride; Naphazolinum [Latin]; Enamine_000333; Alpha-Naphthylmethyl imidazoline; Ciba 2020/R; Nafazolin (TN); Naphazoline (INN); Naphazoline [INN:BAN]; Naphazolinum [INN-Latin]; AK-968/41090774; 2-(1-Naphthylmethyl)-2-imidazoline; 2-(1-Naphthylmethyl)-4,5-dihydro-1H-imidazole; 2-(Naphthyl-(1')-methyl)imidazolin; 2-(Naphthyl-(1')-methyl)imidazolin [German]; 2-(alpha-Naphthylmethyl)-imidazoline; 2-(naphthalen-1-ylmethyl)-4,5-dihydro-1H-imidazole; 4,5-Dihydro-2-(1-naphthylmethyl)imidazole

Indication

Disease Entry	ICD 11	Status	REF
Hyperaemia	9A61-9B7Y	Approved	[1]
Itching	1F28-1G07	Approved	[1]

• Therapeutic Class: Anticancer Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 210.27
  Topological Polar Surface Area (xlogp); 2.1
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1-2 h [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 4 - 8 hours [3]
  Metabolism: The drug is metabolized via the hepatic [2]
• Chemical Identifiers:
  Formula: C14H14N2
  IUPAC Name: 2-(naphthalen-1-ylmethyl)-4,5-dihydro-1H-imidazole
  Canonical SMILES: C1CN=C(N1)CC2=CC=CC3=CC=CC=C32
  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)
  InChIKey: CNIIGCLFLJGOGP-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4436
  ChEBI ID: CHEBI:93363
  CAS Number: 835-31-4
  DrugBank ID: DB06711
  TTD ID: D0O6IZ
  ACDINA ID: D01273

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Agonist	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Hyperaemia
• ICD Disease Classification: 9A61-9B7Y

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dopamine D2 receptor (D2R)	DTT	DRD2	2.50E-02	-0.08	-0.49

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Naphazoline (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Moderate	Decreased metabolism of Naphazoline caused by Methylene blue mediated inhibition of non-CYP450 enzyme.	Acquired methaemoglobinaemia [3A93]	[15]
Levomilnacipran	DMV26S8	Moderate	Increased risk of rapid heart rate by the combination of Naphazoline and Levomilnacipran.	Chronic pain [MG30]	[16]
Ozanimod	DMT6AM2	Moderate	Decreased metabolism of Naphazoline caused by Ozanimod mediated inhibition of non-CYP450 enzyme.	Multiple sclerosis [8A40]	[15]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Sodium citrate anhydrous	E00102	6224	Alkalizing agent; Buffering agent; Complexing agent; Emulsifying agent
Benzalkonium chloride	E00536	21988052	Antimicrobial preservative; Penetration agent; Solubilizing agent; Surfactant
Thimerosal	E00529	16684434	Antimicrobial preservative
Edetate disodium	E00186	8759	Complexing agent
Sodium chloride	E00077	5234	Diluent; Tonicity agent
Water	E00035	962	Solvent
Boric acid	E00152	7628	Antimicrobial preservative; Buffering agent
Camphor	E00060	2537	Antimicrobial preservative; Flavoring agent; Plasticizing agent
Sodium borate	E00511	11954323	Alkalizing agent; Antimicrobial preservative; Buffering agent; Emulsifying agent
Sodium sulhydrate	E00549	23665763	Antimicrobial preservative

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Naphazoline 0.05% solution	0.05%	Solution	Topical
Naphazoline 0.012% solution	0.01%	Solution	Ophthalmic
Naphazoline 0.01% solution	0.01%	Solution	Ophthalmic

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [3] Toxnet: Naphazoline Hydrochloride
• [4] Decongestants in treatment of nasal obstruction. Otolaryngol Pol. 1999;53(3):347-52.
• [5] The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74.
• [6] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [7] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [8] Synthesis and in vitro binding of N-phenyl piperazine analogs as potential dopamine D3 receptor ligands. Bioorg Med Chem. 2005 Jan 3;13(1):77-87.
• [9] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [10] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3639).
• [11] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [12] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [13] Modulatory role of dopamine D2 receptors and fundamental role of L-type Ca2+ channels in the induction of long-term potentiation in the basolateral... Eur J Pharmacol. 2009 Mar 15;606(1-3):90-3.
• [14] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [15] Cusson JR, Goldenberg E, Larochelle P "Effect of a novel monoamine-oxidase inhibitor, moclobemide on the sensitivity to intravenous tyramine and norepinephrine in humans." J Clin Pharmacol 31 (1991): 462-7. [PMID: 2050833]
• [16] Product Information. Cymbalta (duloxetine). Lilly, Eli and Company, Indianapolis, IN.