In vitro antibacterial activity of some systemic and topical antihistaminic preparations

Göçmen, Jülide Sedef; Büyükkoçak, Ünase; Çağlayan, Osman

doi:10.25011/cim.v32i6.10657

Cited by 7 publications

(5 citation statements)

References 12 publications

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“…While other studies have shown an enhancement of antibiotic effects with diphenhydramine against several bacteria [59,60,72,73]. To our knowledge, this is the first demonstration of antibiofilm activity.…”

Section: Discussionsupporting

confidence: 48%

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Cilia Stimulatory and Antibacterial Activities of T2R Bitter Taste Receptor Agonist Diphenhydramine: Insights into Repurposing Bitter Drugs for Nasal Infections

Kuek

McMahon

et al. 2022

Pharmaceuticals

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T2R bitter taste receptors in airway motile cilia increase ciliary beat frequency (CBF) and nitric oxide (NO) production. Polymorphisms in some T2Rs are linked to disease outcomes in chronic rhinosinusitis (CRS) and cystic fibrosis (CF). We examined the expression of cilia T2Rs during the differentiation of human nasal epithelial cells grown at air–liquid interface (ALI). The T2R expression increased with differentiation but did not vary between CF and non-CF cultures. Treatment with Pseudomonas aeruginosa flagellin decreased the expression of diphenhydramine-responsive T2R14 and 40, among others. Diphenhydramine increased both NO production, measured by fluorescent dye DAF-FM, and CBF, measured via high-speed imaging. Increases in CBF were disrupted after flagellin treatment. Diphenhydramine impaired the growth of lab and clinical strains of P. aeruginosa, a major pathogen in CF and CF-related CRS. Diphenhydramine impaired biofilm formation of P. aeruginosa, measured via crystal violet staining, as well as the surface attachment of P. aeruginosa to CF airway epithelial cells, measured using colony-forming unit counting. Because the T2R agonist diphenhydramine increases NO production and CBF while also decreasing bacterial growth and biofilm production, diphenhydramine-derived compounds may have potential clinical usefulness in CF-related CRS as a topical therapy. However, utilizing T2R agonists as therapeutics within the context of P. aeruginosa infection may require co-treatment with anti-inflammatories to enhance T2R expression.

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Section: Discussionsupporting

confidence: 48%

“…DPD was shown to have antibacterial effects against S. aureus [59] and may potentiate the effects of levofloxacin against S. aureus or P. aeruginosa [60]. We showed effects of DPD alone against P. aeruginosa at concentrations that activate T2R receptors.…”

Section: Discussionmentioning

confidence: 63%

Cilia Stimulatory and Antibacterial Activities of T2R Bitter Taste Receptor Agonist Diphenhydramine: Insights into Repurposing Bitter Drugs for Nasal Infections

Kuek

McMahon

et al. 2022

Pharmaceuticals

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“…DPD also disrupts P. aeruginosa growth, biofilm production, and cell attachment of both lab and clinical strains. DPD was shown to have antibacterial effects against S. aureus [28] and may potentiate effects of levofloxacin against S. aureus or P. aeruginosa [29]. We show effects of DPD alone against P. aeruginosa at concentrations that activate T2R receptors.…”

Section: Discussionmentioning

confidence: 63%

Cilia stimulatory and antibacterial activities of bitter receptor agonist diphenhydramine: insights into potential complimentary strategies for CF nasal infections

Kuek

McMahon

et al. 2022

Preprint

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BACKGROUNDBitter compounds increase ciliary beating and nitric oxide (NO) production in nasal epithelial cells through T2Rs in motile cilia. We examined expression of cilia T2Rs and both host and bacterial responses to T2R14 agonist diphenhydramine.METHODUsing cultured human nasal epithelial cells grown at air liquid interface, we measured expression of T2Rs via qPCR. We measured effects of diphenhydramine on ciliary beat frequency via high-speed imaging and nitric oxide production via fluorescent dye DAF-FM. We measured effects of diphenhydramine on growth of lab and clinical strains of Pseudomonas aeruginosa. We measured biofilm formation of P. aeruginosa using crystal violet staining and surface attachment of P. aeruginosa to cystic fibrosis bronchial epithelial (CBFE41o-) cells using CFU counting.RESULTST2R expression increased with mucocilliary differentiation and did not vary between CF and non-CF ALIs. Treatment with P. aeruginosa flagellin decreased expression of diphenhydramine-responsive T2R14 and 40, among other isoforms. Diphenhydramine increased both NO and CBF. Increases in CBF were disrupted after flagellin treatment. Diphenhydramine impaired growth, biofilm production, and surface attachment of P. aeruginosa.CONCLUSIONST2R expression is similar between normal and CF cells but decreases with flagellin treatment. Utilizing T2R agonists as therapeutics within the context of CF, P. aeruginosa infections may require co-treatment with anti-inflammatories to prevent the reduction of T2R expression with TLR activation. T2R agonist diphenhydramine increases NO production and CBF while also decreasing bacterial growth and biofilm production, and thus diphenhydramine or derivate compounds may have potential clinical usefulness in CF infections as a topical therapy.HIGHLIGHTST2R14 agonist diphenhydramine increases nitric oxide production and cilia beatingFlagellin decreases T2R14 expression in primary airway epithelial cellsT2R14 agonist Diphenhydramine inhibits Pseudomonas growth and biofilm formation

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“…Topical diphenhydramine exerts potent antipruritic, anti-inflammatory, antibacterial and anesthetic effects and reinforces the epidermal barrier function. [91011] Ketamine, a high-affinity antagonist of the glutamate N-methyl-D-aspartate receptor, exerts potent antinociceptive and anesthetic properties by various mechanisms especially stimulation of the γ-aminobutyric acid A receptors,[1213] suppresses the release of proinflammatory cytokines through TLR4/2 inhibition, and mimics the biological effects of LDN. [1314] Table 1 summarizes the biological effects of these agents.…”

Section: Discussionmentioning

confidence: 99%

Low-dose naltrexone-induced remission in Hailey–Hailey disease maintained in remission with topical combination of ketamine and diphenhydramine

Sonthalia¹,

Agrawal

Talwar³

et al. 2019

Indian Dermatol Online J

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Recent anecdotal evidence suggests that oral low-dose naltrexone (LDN) is effective for Hailey–Hailey disease (HHD) but suffers the limitation of immediate relapse following cessation of the medication. With lack of safety data on long-term administration of LDN, we explored the utility of a topical diphenhydramine/ketamine (DK) cream in maintaining the remission achieved with LDN. A 42-year-old male with treatment-refractory HHD remitted with 5 mg naltrexone/day but relapsed on stopping the drug. Symptoms abated after restarting LDN. The impact of regular twice-a-day application of a specially formulated DK cream containing diphenhydramine (2% w/w) and ketamine (1% w/w) over the affected areas on maintenance of remission was explored till the next relapse. Our approach enabled dose reduction of naltrexone to 3 mg/day without loss of treatment benefit. After 3-month overlap of naltrexone and DK cream, withdrawal of naltrexone maintained remission with only the topical regime with no adverse effects till 4 months of follow-up. The use of topical agents with anti-inflammatory, antipruritic, antinociceptive, and naltrexone-mimicking properties merits exploration as an option to provide short but significant period of naltrexone-free maintenance of remission to patients with HHD.

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In vitro antibacterial activity of some systemic and topical antihistaminic preparations

Cited by 7 publications

References 12 publications

Cilia Stimulatory and Antibacterial Activities of T2R Bitter Taste Receptor Agonist Diphenhydramine: Insights into Repurposing Bitter Drugs for Nasal Infections

Cilia Stimulatory and Antibacterial Activities of T2R Bitter Taste Receptor Agonist Diphenhydramine: Insights into Repurposing Bitter Drugs for Nasal Infections

Cilia stimulatory and antibacterial activities of bitter receptor agonist diphenhydramine: insights into potential complimentary strategies for CF nasal infections

Low-dose naltrexone-induced remission in Hailey–Hailey disease maintained in remission with topical combination of ketamine and diphenhydramine

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