Methadone: Antimicrobial Activity and Interaction with Antibiotics

Sheagren, John N.; Barsoum, I. S.; Lin, Melody Y. C.

doi:10.1128/aac.12.6.748

Cited by 5 publications

(5 citation statements)

References 6 publications

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“…While the speci c effects of these compounds require further investigation, some, like n-hexadecanoic acid and 5-eicosene, have shown potential antioxidant activity (Iqbal & Bhanger, 2006;Kubo et al, 1994). Additionally, 3-phenylthiane, Soxide has demonstrated anti-in ammatory properties in preclinical studies (Chen et al, 2010), and methadone N-oxide exhibits potential antimicrobial activity against speci c bacteria (Sheagren et al, 1977). Notably, compounds like 5-methyl-2-phenylindolizine and (1-ethylbuta-1,3-dienyl)benzene have shown interactions with the nervous system, warranting further investigation into their speci c effects (Li et al, 2007;Yagi et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Towards a Natural Treatment for Mania: Red Onion Husk Extract Modulates Neuronal Resilience, Redox Signalling, and Glial Activation.

Ekeanyanwu,

EKEANYANWU,

UGOCHUKWU

2024

Preprint

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Background Red onion husk, a readily available agricultural waste material, contains diverse bioactive compounds with potential health benefits. This study aimed to assess the safety and therapeutic potential of red onion husk extract in managing manic-like symptoms and associated neurochemical dysfunctions. Methods Acute and repeated oral dose studies were conducted in mice and rats to evaluate the safety profile of the extract. FT-IR analysis identified functional groups in the extract, while GC-MS analysis identified specific bioactive compounds in the flavonoid-rich fraction. A ketamine-induced manic behaviour model in Wistar rats was employed to assess the extract's efficacy in attenuating manic-like symptoms. Behavioural and neurochemical analyses were performed to further investigate the extract's effects. Results The extract demonstrated a favourable safety profile in both acute and repeated dose studies. FT-IR analysis revealed a complex mixture of organic compounds, including hydroxyl groups, alkynes/nitriles, aromatic and non-aromatic C = C bonds, amines, and polysaccharides. GC-MS analysis identified 17 bioactive compounds, including five-methyl-2-phenylindolizine, methadone N-oxide, and 3-phenylthiane, S-oxide. Ketamine administration significantly increased oxidative stress markers, TBARS, and suppressed antioxidant enzyme activities (SOD, GPx, CAT) in both the cerebral cortex and hippocampus, alongside elevated acetylcholinesterase (AchE) activity, indicating enhanced neuronal excitability. Pre-treatment with FRF (25 mg/kg) effectively mitigated ketamine-induced oxidative stress, as evidenced by reduced TBARS levels and partially restored SOD and GPx activities. Interestingly, FRF significantly increased CAT activity (p < 0.001), potentially suggesting an additional compensatory mechanism. Notably, FRF pre-treatment also counteracted ketamine-upregulated AchE activity, offering neuroprotection against heightened neuronal excitability. Conclusion Red onion husk extract exhibits a favourable safety profile and exerts potent antioxidant and neuroprotective effects, possibly through modulating Nrf2 signalling pathways. Its ability to counteract ketamine-induced oxidative stress and neuronal hyperactivity highlights its potential as a complementary therapeutic strategy for managing manic episodes in bipolar disorder. Further research is warranted to elucidate the precise molecular mechanisms underlying FRF's action and explore its clinical efficacy in human studies.

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Section: Discussionmentioning

confidence: 99%

Towards a Natural Treatment for Mania: Red Onion Husk Extract Modulates Neuronal Resilience, Redox Signalling, and Glial Activation.

Ekeanyanwu,

EKEANYANWU,

UGOCHUKWU

2024

Preprint

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“…Together with carbamazepine, it caused toxic effects in intestinal epithelial cells in vitro and inhibited the growth of several species of bacteria representing a healthy digestive system in children up to 9 years of age (such as Ruminococcus gnavus, Clostridium ramosum, and Roseburia intestinalis) and patients with drug-resistant epilepsy (including "anti-epileptic" Parabacteroides species), while the growth of Staphylococcus caprae, Dorea longicatena, E. coli, and Klebsiella aerogenes growth was enhanced (Ilhan et al, 2022). Tramadol has strong in vitro bactericidal activity against E. coli and S. epidermidis and weak antimicrobial activity against S. aureus and P. aeruginosa (Tamanai-Shacoori et al, 2007), and methadone against S. aureus, P. aeruginosa and S. marcescens (Sheagren et al, 1977). Tramadol administered at concentrations of 12.5 and 25 mg/ml to BALB mice infected with Staphylococcus aureus and Pseudomonas aeruginosa induced a reduction in wound diameter (by inflammation induction and phagocytic activity) caused by S. aureus (Farzam et al, 2018).…”

Section: Analgesics and Anticonvulsantsmentioning

confidence: 99%

Clinical significance of microbiota changes under the influence of psychotropic drugs. An updated narrative review

et al. 2023

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Relationship between drugs and microbiota is bilateral. Proper composition thus function of microbiota is a key to some medications used in modern medicine. However, there is also the other side of the coin. Pharmacotherapeutic agents can modify the microbiota significantly, which consequently affects its function. A recently published study showed that nearly 25% of drugs administered to humans have antimicrobial effects. Multiple antidepressants are antimicrobials,. and antibiotics with proven antidepressant effects do exist. On the other hand, antibiotics (e.g., isoniaside, minocycline) confer mental phenotype changes, and adverse effects caused by some antibiotics include neurological and psychological symptoms which further supports the hypothesis that intestinal microbiota may affect the function of the central nervous system. Here we gathered comprehensively data on drugs used in psychiatry regarding their antimicrobial properties. We believe our data has strong implications for the treatment of psychiatric entities. Nevertheless the study of ours highlights the need for more well-designed trials aimed at analysis of gut microbiota function.

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“…The results showed that methadone has a bigger antibacterial effect against Staphylococcus aureus than against the two other Gram-negative organisms tested, but only at supraphysiological concentrations. Moreover, it has a partial or total synergistic effect with other antimicrobial agents like nafcillin or gentamicin [16].…”

Section: Opioidsmentioning

confidence: 99%

Antimicrobial Properties on Non-Antibiotic Drugs in the Era of Increased Bacterial Resistance

et al. 2020

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In recent years, due to the dramatic increase in and global spread of bacterial resistance to a number of commonly used antibacterial agents, many studies have been directed at investigating drugs whose primary therapeutic purpose is not antimicrobial action. In an era where it is becoming increasingly difficult to find new antimicrobial drugs, it is important to understand these antimicrobial effects and their potential clinical implications. Numerous studies report the antibacterial activity of non-steroidal anti-inflammatory drugs, local anaesthetics, phenothiazines such as chlorpromazine, levomepromazine, promethazine, trifluoperazine, methdilazine and thioridazine, antidepressants, antiplatelets and statins. Several studies have explored a possible protective effect of statins inreducing the morbidity and mortality of many infectious diseases. Various non-antibiotic agents exhibit antimicrobial activity via multiple and different mechanisms of action. Further studies are required in the field to further investigate these antimicrobial properties in different populations. This is of paramount importance in the antimicrobial resistance era, where clinicians have limited therapeutic options to combat problematic infections.

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Methadone: Antimicrobial Activity and Interaction with Antibiotics

Cited by 5 publications

References 6 publications

Towards a Natural Treatment for Mania: Red Onion Husk Extract Modulates Neuronal Resilience, Redox Signalling, and Glial Activation.

Towards a Natural Treatment for Mania: Red Onion Husk Extract Modulates Neuronal Resilience, Redox Signalling, and Glial Activation.

Clinical significance of microbiota changes under the influence of psychotropic drugs. An updated narrative review

Antimicrobial Properties on Non-Antibiotic Drugs in the Era of Increased Bacterial Resistance

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