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dc.contributor.authorHarvey, Brian H.
dc.contributor.authorDuvenhage, Ingrid
dc.contributor.authorViljoen, Francois
dc.contributor.authorScheepers, Nellie
dc.contributor.authorBrink, Christiaan B.
dc.contributor.authorPetzer, Jacobus P.
dc.contributor.authorMalan, Sarel F.
dc.date.accessioned2012-02-29T09:49:41Z
dc.date.available2012-02-29T09:49:41Z
dc.date.issued2010en_US
dc.identifier.citationHarvey, B.H. et al. 2010. Role of monoamine oxidase, nitric oxide synthase and regional brain monoamines in the antidepressant-like effects of methylene blue and selected structural analogues. Biochemical pharmacology, 80(10):1580-1591. [https://doi.org/10.1016/j.bcp.2010.07.037]en_US
dc.identifier.issn1873-2968en_US
dc.identifier.issn0006-2952 (Online)en_US
dc.identifier.urihttp://hdl.handle.net/10394/5917
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0006295210005757
dc.identifier.urihttps://doi.org/10.1016/j.bcp.2010.07.037
dc.description.abstractDual action antidepressants have important therapeutic implications. Methylene blue (MB), a charged compound structurally related to tricyclic antidepressants, acts on both monoamine oxidase (MAO) and the nitric oxide (NO)-cGMP pathway, and has demonstrated antidepressant activity in rodents. We investigated the antidepressant properties of MB and selected structural analogues and whether their actions involve MAO, NO synthase (NOS) and regional brain monoamines. Acute imipramine (IMI, 15 mg/kg), saline, MB, acriflavine (ACR), methylene green (MG), methylene violet (MV), thionine (THI) and tacrine (TAC) (1-60 mg/kg i.p.) were tested for antidepressant activity in the forced swim test (FST), as well as MAO-A/B inhibitory activity. Active antidepressant compounds were subsequently studied at their most effective dose during sub-chronic treatment, followed by behavioural sampling in the FST and assay of cortico-limbic monoamines and hippocampal nitrate (for NOS activity). Only IMI, MB (15, 30, 60 mg/kg) and MG (7.5, 25, 40 mg/kg) reduced immobility in the acute FST. MB, MG and ACR were potent inhibitors of especially MAO-A. Following sub-chronic treatment, IMI (15 mg/kg) increased noradrenergic behaviour in the FST, while MB (15 mg/kg) and MG (15 mg/kg) enhanced serotonergic behaviour. MB and MG bolstered cortico-limbic serotonin (5HT) levels and to a lesser extent l-norepinephrine (l-NE), but did not significantly alter regional dopamine (DA) levels. MB, and to lesser degree MG, reduced hippocampal nitrate levels. MB and MG present with structure-specific antidepressant-like effects following acute and sub-chronic treatment, possibly involving NOS and MAO-A inhibition and cortico-limbic 5HT and l-NE release. A role for MAO-B and DA appears minimal
dc.language.isoen
dc.publisherElsevieren_US
dc.subjectDual action
dc.subjectMethylene blue
dc.subjectStructural analogues
dc.subjectAntidepressant
dc.subjectMonoamine oxidase
dc.subjectNitric oxide
dc.subjectSerotonin
dc.subjectNorepinephrine
dc.subjectDopamine
dc.titleRole of monoamine oxidase, nitric oxide synthase and regional brain monoamines in the antidepressant-like effects of methylene blue and selected structural analoguesen_US
dc.contributor.researchID11083417 - Harvey, Brian Herbert
dc.contributor.researchID10073892 - Brink, Christiaan Beyers
dc.contributor.researchID10199667 - Malan, Sarel Francois
dc.contributor.researchID10727388 - Petzer, Jacobus Petrus
dc.contributor.researchID11775416 - Viljoen, Francois Petrus
dc.contributor.researchID13080121 - Duvenhage, Ingrid
dc.contributor.researchID11311827 - Scheepers, Johanna Cornelia


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