Evaluation of a New Topical Anesthetic, Dyclonine Hydrochloride

Shelmire, Bedford

doi:10.1001/archderm.1955.01540300050013

Cited by 13 publications

(8 citation statements)

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“…S3 ). Since dyclonine is used primarily as a topical anesthetic ( 13 ), we tested whether dyclonine induced systemic anesthesia when dosed systemically at doses relevant for FXN induction. We measured hot plate response times in mice dosed with 3 mg/kg dyclonine i.p., and observed no delay in hot plate response over 1.5 h ( Supplementary Material, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…One of the strongest hit in terms of efficacy and potency at protecting from diamide stress was dyclonine, the active agent in Sucrets. Dyclonine was initially characterized as an anti-epileptic ( 56 ), but through its sodium channel inhibitory properties it has been used for anesthesia since 1955 ( 13 ). Dyclonine's protective effect could potentially be due to multiple mechanisms, including increased mitochondrial biogenesis, Fe/S cluster biogenesis, iron binding or others.…”

Section: Discussionmentioning

confidence: 99%

“…The cell model identified dyclonine, and we have shown that it induces FXN in cells, animal models and FA patients through a novel mechanism. 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 ).…”

Section: Introductionmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…One per cent dyclonine was definitely more effec¬ tive than 0.5% dyclonine and comparable to 5% cocaine. 4. It is our opinion that no topical anes¬ thetic should be considered to be without hazard.…”

Section: Toxic Reactionsmentioning

confidence: 97%

“…Clinically the drug has been used in the eye, mouth, bronchi, urethra, and on skin. [2][3][4][5][6][7] Dyclonine is chemically different from any of the local anesthetics in use today.f The compound is a white crystalline powder soluble at a 2% concentration in water.…”

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confidence: 99%