Effect of Afobazole on Mitochondrial Monoamine Oxidase A Activity In Vitro

Voronin, M. V.; Aksenova, L N; Buneena, O. A.; Медведев, А. Е.

doi:10.1007/s10517-009-0630-z

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…The effects of afobazole on DA and DOPAC content and latency to fall in the rotarod test were less affected by BD-1047 pre-administration than PRE-084. These observations may argue for the existence of additional molecular mechanisms, in addition to Sigma1Rs, that mediate the neuroprotective effect of afobazole 38,49,50 . Thus, the lack of significant elevation in DOPAC content, along with the normalization of DA levels after afobazole treatment, suggests the inhibition of MAO-A by the drug 49 , which may facilitate the neuroprotective action of afobazole on neurons of the nigrostriatal pathway 51 .…”

Section: Discussionmentioning

confidence: 99%

“…These observations may argue for the existence of additional molecular mechanisms, in addition to Sigma1Rs, that mediate the neuroprotective effect of afobazole 38,49,50 . Thus, the lack of significant elevation in DOPAC content, along with the normalization of DA levels after afobazole treatment, suggests the inhibition of MAO-A by the drug 49 , which may facilitate the neuroprotective action of afobazole on neurons of the nigrostriatal pathway 51 . The results obtained in our study are consistent with previously published data on the cytoprotective and neuroprotective effects of afobazole, demonstrating the role of Sigma1Rs in the activation of antiparkinsonian mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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Chaperone Sigma1R mediates the neuroprotective action of afobazole in the 6-OHDA model of Parkinson’s disease

Voronin

Kadnikov

Воронков

et al. 2019

Sci Rep

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Parkinson’s disease (PD) is a progressive neurodegenerative disease with limited treatment options. Therefore, the identification of therapeutic targets is urgently needed. Previous studies have shown that the ligand activation of the sigma-1 chaperone (Sigma1R) promotes neuroprotection. The multitarget drug afobazole (5-ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole dihydrochloride) was shown to interact with Sigma1Rs and prevent decreases in striatal dopamine in the 6-hydroxydopamine (6-OHDA)-induced parkinsonism model. The aim of the present study was to elucidate the role of Sigma1Rs in afobazole pharmacological activity. Using ICR mice we found that administration of afobazole (2.5 mg/kg, i.p.) or selective agonist of Sigma1R PRE-084 (1.0 mg/kg, i.p.) over 14 days normalizes motor disfunction and prevents decreases in dopamine in the 6-OHDA-lesioned striatum. Afobazole administration also prevents the loss of TH + neurons in the substantia nigra. The pre-administration of selective Sigma1R antagonist BD-1047 (3.0 mg/kg, i.p.) abolishes the activity of either afobazole or PRE-084, as determined using the rotarod test and the analysis of striatal dopamine content. The current study demonstrates the contribution of Sigma1Rs in the neuroprotective effect of afobazole in the 6-OHDA model of Parkinson’s disease and defines the therapeutic perspective of Sigma1R agonists in the clinic.

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