Dequalinium

Identification

Summary

Dequalinium is a quaternary ammonium cation antimicrobial agent used to treat common infections of the mouth and throat, as well as vaginal candidiasis.

Generic Name

Dequalinium

DrugBank Accession Number

DB04209

Background

Dequalinium is an antibacterial agent with multi-targeted actions. It also possesses antifungal, antiparasitic, antiviral, anticancer, and neuroprotective properties.⁹ It is a quaternary ammonium compound,¹⁰ as it consists of an amphipathic cation with two aminoquinaldinium rings at both ends of a long hydrophobic hydrocarbon chain. Due to its flexible structure, dequalinium was investigated to build drug and gene delivery systems.⁹

First used as an antiseptic and disinfectant in the 1950s, dequalinium is still found in various OTC products to treat conditions of oral infections and inflammation.⁹ It is also used in vaginal tablets to treat bacterial vaginosis.¹⁰

Type

Small Molecule

Groups

Approved, Investigational

Structure

Similar Structures

Weight: Average: 456.6654
Monoisotopic: 456.3252973
Chemical Formula: C₃₀H₄₀N₄

Synonyms

1,1'-(1,10-Decanediyl)bis(4-amino-2-methylquinolinium) dichloride
1,1'-Decamethylenebis(4-aminoquinaldinium chloride)
Decamethylenebis(4-aminoquinaldinium chloride)

External IDs

LSM-5846

Pharmacology

Indication

Dequalinium is used in several OTC products to treat mouth infections and inflammation, such as tonsillitis, pharyngitis, and gingivitis.⁹ As vaginal tablets, dequalinium is indicated for the treatment of bacterial vaginosis in adult women under 55 years of age.¹⁰

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Associated Conditions

Associated Therapies

Oropharyngeal antisepsis

Contraindications & Blackbox Warnings

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Pharmacodynamics

In vitro, dequalinium possesses antimicrobial activity against gram-positive and gram-negative bacteria, yeasts, and protozoa.⁶ Dequalinium has a rapid bactericidal and fungicidal action.¹ The antiparasitic and antiviral properties of dequalinium have also been noted. For example, dequalinium can bind to the membrane-proximal external region (MPER) of the spike envelope of the human immunodeficiency virus HIV-1.⁹

As with other quaternary ammonium compounds similar to dequalinium, gram-positive bacteria are more sensitive to dequalinium than gram-negative bacteria.^6,10 The bactericidal and fungicidal effects of dequalinium can occur within 30 to 60 minutes.⁷ According to in vitro studies, the minimal inhibitory concentration (MIC) for dequalinium against relevant vaginal pathogens ranges from 0.2 to ≥ 1024 µg/mL.¹⁰

There is evidence that dequalinium exhibits anticancer activity in human leukemia cells: dequalinium induces a cytotoxic effect by altering redox balance, downregulating Raf/MEK/ERK1/2 and PI3K/Akt signalling pathways, and promoting apoptosis of leukemic cells.^3,4,5 Dequalinium was also shown to block small conductance Ca²⁺-activated K⁺ channels, called SK channels, which are often expressed in some cancer cells to play a role in cell proliferation and migration.⁹ One study showed that dequalinium reduced macrophage motility in mice, inhibiting macrophage infiltration of irradiated tumours and attenuating local metastasis.²

Interestingly, dequalinium was shown to modulate and induce self-oligomerization of alpha-synuclein, a synaptic protein known to cause aggregates in several neurodegenerative disorders. This finding highlights the neuroprotective actions of dequalinium; however, further investigations are warranted as dequalinium is a neurotoxic agent.⁹

Mechanism of action

Dequalinium has multiple modes of action. Dequalinium absorbs into the bacterial cell surface and diffuses through the cell wall, disrupting bacterial cell permeability.^6,9 It is taken up by the bacteria rapidly.⁹ Once in the bacteria, dequalinium denatures proteins involved in the respiratory chain and glycolysis of bacteria, interfering with bacterial cell metabolism and ribosomal protein synthesis.^1,6,9 By inhibiting bacterial F1-ATPase, dequalinium inhibits mitochondrial ATP synthesis and blocks glucose metabolism. These molecular actions ultimately deplete bacterial energy sources.¹ As dequalinium accumulates in the mitochondria, it is considered a mitochondrial poison.^8,9

Dequalinium can also precipitate nucleic acids, as it can intercalate one of its quinoline chromophores between DNA base pairs.^1,9 Depending on the drug concentration, dequalinium can lyse the bacterial cell by promoting osmotic imbalance.^1,6

Target	Actions	Organism
AE3 ubiquitin-protein ligase XIAP	antagonist inhibitor	Humans
UcGMP-gated cation channel alpha-1	blocker	Humans
UCalcium-activated potassium channel subunit alpha-1	inhibitor	Humans
UHTH-type transcriptional regulator QacR	regulator	Staphylococcus aureus
UResponse regulator RamR	regulator	Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)
UCalmodulin	antagonist	Humans
USmall conductance calcium-activated potassium channel protein 3	blocker	Humans
UProtein kinase C	inhibitor	Humans
UAlpha-synuclein	modulator	Humans
UL-cysteine:1D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside ligase	inhibitor	Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra)

Absorption

Following vaginal administration, dequalinium is not readily absorbed into the systemic circulation. The concentration of dequalinium chloride in vaginal fluid was 2000 to 4000 mg/L in vitro after dissolution of one vaginal tablet (equivalent of 10 mg dequalinium chloride) in an estimated 2.5 to 5 mg/L of vaginal fluid.¹⁰

Volume of distribution