Antimicrobial Properties of Dyclonine Hydrochloride, A New Topical Anesthetic

Florestano, H. J.; Bahler, M.E.

doi:10.1002/jps.3030450514

Cited by 20 publications

(5 citation statements)

References 11 publications

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“…Dyclonine is an oral anesthetic used to provide topical anesthesia to mucous membranes through sodium channel inhibition ( 13 ). It is the active ingredient in Sucrets, an over-the-counter throat lozenge, and has been in use for over 50 years ( 14 ). Additionally, dyclonine is used during dental examinations and procedures to numb mucous membranes of the mouth ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's ataxia

Sahdeo¹,

Scott²,

McMackin³

et al. 2014

Human Molecular Genetics

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Inherited deficiency in the mitochondrial protein frataxin (FXN) causes the rare disease Friedreich's ataxia (FA), for which there is no successful treatment. We identified a redox deficiency in FA cells and used this to model the disease. We screened a 1600-compound library to identify existing drugs, which could be of therapeutic benefit. We identified the topical anesthetic dyclonine as protective. Dyclonine increased FXN transcript and FXN protein dose-dependently in FA cells and brains of animal models. Dyclonine also rescued FXN-dependent enzyme deficiencies in the iron–sulfur enzymes, aconitase and succinate dehydrogenase. Dyclonine induces the Nrf2 [nuclear factor (erythroid-derived 2)-like 2] transcription factor, which we show binds an upstream response element in the FXN locus. Additionally, dyclonine also inhibited the activity of histone methyltransferase G9a, known to methylate histone H3K9 to silence FA chromatin. Chronic dosing in a FA mouse model prevented a performance decline in balance beam studies. A human clinical proof-of-concept study was completed in eight FA patients dosed twice daily using a 1% dyclonine rinse for 1 week. Six of the eight patients showed an increase in buccal cell FXN levels, and fold induction was significantly correlated with disease severity. Dyclonine represents a novel therapeutic strategy that can potentially be repurposed for the treatment of FA.

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Section: Introductionmentioning

confidence: 99%

Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's ataxia

Sahdeo¹,

Scott²,

McMackin³

et al. 2014

Human Molecular Genetics

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“…Bacteriological study revealed that compounds of this series have significant antimicrobial action in vitro (9).…”

Section: Discussionmentioning

confidence: 96%

Alkoxy Derivatives of β-Piperidinopropiophenone and Related Compounds**Research Department, Pitman-Moore Co., Division of Allied Laboratories, Inc., Indianpolis, Ind.

Bockstahler

Wright

1957

Journal of the American Pharmaceutical Association (Scientific

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“…As a clinical anesthetic, dyclonine is characterized by rapid onset of effect, lack of systemic toxicity, and a low index of sensitization (Florestano & Bahler, 1956). Its topical application (0.5% or 1% dyclonine hydrochloride contained in the topical solution, i.e., ~30.7 mM at a dose of 1%, according to the United States Pharmacopeia) rapidly relieves itching and pain in patients, by ameliorating inflamed, excoriated and broken lesions on mucous membranes and skin (Morginson et al, 1956).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine

Liu

Wang

Wei

et al. 2021

eLife

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The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. We here report that mouse and human TRPV3 channel is targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.

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Antimicrobial Properties of Dyclonine Hydrochloride, A New Topical Anesthetic

Cited by 20 publications

References 11 publications

Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's ataxia

Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's ataxia

Alkoxy Derivatives of β-Piperidinopropiophenone and Related Compounds**Research Department, Pitman-Moore Co., Division of Allied Laboratories, Inc., Indianpolis, Ind.

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine

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