P.2.e.001 Methylene blue for residual symptoms and for cognitive dysfunction in bipolar disorder: results of a double-blind trial

Alda, Martin; MacQueen, Glenda; McKinnon, Moira; Garnham, Julie; MacLellan, S.; Hájek, Tomáš; O′Donovan, Claire; Sokolenko, M. O.

doi:10.1016/s0924-977x(11)70674-5

Cited by 4 publications

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“…The inhibition of MAO-A as well as non-selective inhibition of NOS and guanylate cyclase may thus describe a dual action that is responsible for MB's antidepressant effect Luo et al, 1995). As an extension of these actions, MB has shown promising antidepressant and anxiolytic qualities in bipolar disorder (Naylor et al, 1986(Naylor et al, , 1987Alda et al, 2011). Considering the role of mitochondrial dysfunction and oxidative stress in the pathology of depression, MB's ability to enhance mitochondrial function by cycling between the reduced leucomethylene blue (leucoMB) and the oxidized MB states will inhibit the production of superoxide by competing with molecular oxygen (Atamna and Kumar, 2010;Oz et al, 2009;Visarius et al, 1997;Kelner et al, 1988;Salaris et al, 1991), and in this way counter the atrophic changes that complicate this illness (Duman and Monteggia, 2006;Harvey, 2008;Krishnan and Nestler, 2008).…”

Section: Introductionmentioning

confidence: 99%

Azure B and a synthetic structural analogue of methylene blue, ethylthioninium chloride, present with antidepressant-like properties

et al. 2014

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Section: Introductionmentioning

confidence: 99%

Azure B and a synthetic structural analogue of methylene blue, ethylthioninium chloride, present with antidepressant-like properties

et al. 2014

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Methylene blue and its analogues as antidepressant compounds

et al. 2017

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Methylene Blue (MB) is considered to have diverse medical applications and is a well-described treatment for methemoglobinemias and ifosfamide-induced encephalopathy. In recent years the focus has shifted to MB as an antimalarial agent and as a potential treatment for neurodegenerative disorders such as Alzheimer's disease. Of interest are reports that MB possesses antidepressant and anxiolytic activity in pre-clinical models and has shown promise in clinical trials for schizophrenia and bipolar disorder. MB is a noteworthy inhibitor of monoamine oxidase A (MAO-A), which is a well-established target for antidepressant action. MB is also recognized as a non-selective inhibitor of nitric oxide synthase (NOS) and guanylate cyclase. Dysfunction of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) cascade is strongly linked to the neurobiology of mood, anxiety and psychosis, while the inhibition of NOS and/or guanylate cyclase has been associated with an antidepressant response. This action of MB may contribute significantly to its psychotropic activity. However, these disorders are also characterised by mitochondrial dysfunction and redox imbalance. By acting as an alternative electron acceptor/donor MB restores mitochondrial function, improves neuronal energy production and inhibits the formation of superoxide, effects that also may contribute to its therapeutic activity. Using MB in depression co-morbid with neurodegenerative disorders, like Alzheimer's and Parkinson's disease, also represents a particularly relevant strategy. By considering their physicochemical and pharmacokinetic properties, analogues of MB may provide therapeutic potential as novel multi-target strategies in the treatment of depression. In addition, low MAO-A active analogues may provide equal or improved response with a lower risk of adverse effects.

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Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase

Petzer

Harvey

Wegener

et al. 2012

Toxicology and Applied Pharmacology

105

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P.2.e.001 Methylene blue for residual symptoms and for cognitive dysfunction in bipolar disorder: results of a double-blind trial

Cited by 4 publications

References 0 publications

Azure B and a synthetic structural analogue of methylene blue, ethylthioninium chloride, present with antidepressant-like properties

Azure B and a synthetic structural analogue of methylene blue, ethylthioninium chloride, present with antidepressant-like properties

Methylene blue and its analogues as antidepressant compounds

Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase

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