DYCLONINE

US Approved OTC

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H27NO2
Molecular Weight	289.4125
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCOC1=CC=C(C=C1)C(=O)CCN2CCCCC2

InChI

InChIKey=BZEWSEKUUPWQDQ-UHFFFAOYSA-N

InChI=1S/C18H27NO2/c1-2-3-15-21-17-9-7-16(8-10-17)18(20)11-14-19-12-5-4-6-13-19/h7-10H,2-6,11-15H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14375392/
Curator's Comment: Description was created based on several sources, including http://www.sucrets.com/sore-throat-remedies | https://www.ncbi.nlm.nih.gov/pubmed/25113747 | https://www.drugs.com/monograph/dyclonine-hydrochloride.html | https://www.ncbi.nlm.nih.gov/pubmed/19148544 | https://www.ncbi.nlm.nih.gov/pubmed/25174315 | https://www.ncbi.nlm.nih.gov/pubmed/25113747

Dyclonine is an local anesthetic used to provide topical anesthesia to mucous membranes through sodium channel inhibition. It is the active ingredient in Sucrets, an over-the-counter throat lozenge. It has been used as a local anesthetic agent prior to laryngoscopy, bronchoscopy, esophagoscopy, or endotracheal intubation. However, oral solutions no longer are commercially available in the US. Recently, additional activities of dyclonine have been discovered. Dyclonine represents a novel therapeutic strategy that can potentially be repurposed for the treatment of Friedreich's ataxia. Dyclonine enhances the cytotoxic effect of proteasome inhibitors on cancer and multiple myeloma cells.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sodium channel protein type II alpha subunit 27 Target ID: CHEMBL4187 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25113747	Inhibitor 8504	6.0 µM [IC50]
Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 7 Target ID: CHEMBL6032 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25113747	Inhibitor 8504
Nuclear factor erythroid 2-related factor 2 15 Target ID: CHEMBL1075094 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25113747	Activator 1447
Aldehyde dehydrogenase dimeric NADP-preferring 2 Target ID: CHEMBL3578 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22021038	Inhibitor 8504	76.0 µM [IC50]
Aldehyde dehydrogenase 8 Target ID: CHEMBL1935 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22021038	Inhibitor 8504	35.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Sore throat 18 Sources: http://www.sucrets.com/sore-throat-remedies	Primary	Approved 8583	SUCRETS Approved Use temporarily relieves: occasional minor irritation, pain, sore throat and sore mouth cough associated with a cold or inhaled irritants
Cancer 609 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19148544 https://www.ncbi.nlm.nih.gov/pubmed/25174315	Primary	Basic research	Unknown Approved Use Unknown
Pain 619 Sources: https://www.drugs.com/monograph/dyclonine-hydrochloride.html	Primary	Approved 8583	DYCLONE Approved Use Has been used as a local anesthetic agent prior to laryngoscopy, bronchoscopy, esophagoscopy, or endotracheal intubation. However, oral solutions no longer are commercially available in the US.
Friedreich ataxia 12 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25113747	Primary	Not Provided 511	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
42.17 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22305084/	20 μg/cm² single, topical dose: 20 μg/cm² route of administration: Topical experiment type: SINGLE co-administered:		DYCLONINE plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
152.81 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22305084/	20 μg/cm² single, topical dose: 20 μg/cm² route of administration: Topical experiment type: SINGLE co-administered:		DYCLONINE plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.85 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22305084/	20 μg/cm² single, topical dose: 20 μg/cm² route of administration: Topical experiment type: SINGLE co-administered:		DYCLONINE plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
8 mg single, oral Recommended Dose: 8 mg Route: oral Route: single Dose: 8 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2376253/	healthy, adult Health Status: healthy Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/2376253/	Sources: https://pubmed.ncbi.nlm.nih.gov/2376253/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
ALDH3 2

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
ALDH3 2	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/30333913/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4724	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4724
ChemicalBook	CB4475550	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4475550
eMolecules	1202842	https://www.emolecules.com/cgi-bin/more?vid=1202842
ZINC	ZINC000001530940	http://zinc15.docking.org/substances/ZINC000001530940

PubMed

Title	Date	PubMed
Applications of microarray technology in breast cancer research.	2001	11305951
Airway anesthesia alone does not explain attenuation of histamine-induced bronchospasm by local anesthetics: a comparison of lidocaine, ropivacaine, and dyclonine.	2001 Mar	11374600
Enigmatic pain referred to the teeth and jaws.	2001 Mar-Apr	12004699
Both local anesthetics and salbutamol pretreatment affect reflex bronchoconstriction in volunteers with asthma undergoing awake fiberoptic intubation.	2002 Dec	12459670
Chemical genomics in yeast.	2004	15345040
The uses of genome-wide yeast mutant collections.	2004	15239820
Solid-state characterization of falicaine hydrochloride and isomorphic dyclonine hydrochloride. Part IV. Crystal polymorphism of local anaesthetic drugs.	2005 Jul-Aug	15896948
Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans.	2007 Jun	17604452
Lidocaine exerts its effect on induced bronchospasm by mitigating reflexes, rather than by attenuation of smooth muscle contraction.	2007 Mar	17390422
[The use of 1% dyclonine and local cryoanesthesia plus pulp vitality test agent in taking dental X-ray film].	2008 Feb	18360665
Functional toxicogenomics: mechanism-centered toxicology.	2010	21614174
Microneedle pretreatment improves efficacy of cutaneous topical anesthesia.	2010 Feb	20159380
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003

Patents

Sample Use Guides

In Vivo Use Guide

Oral/Throat Pain 1 lozenge (1.2, 2, or 3 mg); repeat after 2 hours if necessary Usual Dosage Use the lowest dose needed to provide effective anesthesia Mouth sores: 5-10 mL of 0.5% or 1% to oral mucosa (swab or swish and then spit) 3-4 times/day as needed; maximum single dose: 200 mg (40 mL of 0.5% solution or 20 mL of 1% solution) Bronchoscopy: Use 2 mL of the 1% solution or 4 mL of the 0.5% solution sprayed onto the larynx and trachea every 5 minutes until the reflex has been abolished

Route of Administration: Topical

In Vitro Use Guide

Dyclonine enhances the cytotoxic effects of proteasome inhibitor MG132 on breast cancer cells in low micromolar range

Name

Type

Language

1-PROPANONE, 1-(4-BUTOXYPHENYL)-3-(1-PIPERIDINYL)

Preferred Name

English

DYCLONINE

Official Name

English

4'-BUTOXY-3-PIPERIDINOPROPIOPHENONE

Systematic Name

English

Dyclonine [WHO-DD]

Common Name

English

DYCLONINE [MI]

Common Name

English

dyclonine [INN]

Common Name

English

DYCLONINE [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C245