High impact information on Lopac-R-107

• Here we describe how reversible and selective inhibitors of MAO-A and MAO-B [Ro 41-1049 and Ro 19-6327 (lazabemide), respectively] can be used, as tritiated radioligands, to map the distribution and abundance of the enzymes in microscopic regions of the rat CNS and peripheral organs, and human brain by quantitative enzyme radioautography [1].
• These mutants also showed a distinct shift in sensitivity for the MAO A- and B-selective inhibitors Ro 41-1049 and Ro 16-6491 [2].
• The existence of a Ro 41-1049 adduct reversibly bound to the enzyme active site might explain the inhibition mechanism of this compound [3].
• The structurally diverse MAO inhibitors Ro 16-6491 (selective for MAO-B) and Ro 41-1049 (selective for MAO-A), as well as the other psychotropic drugs (desipramine, cocaine, reserpine and haloperidol) displaced the binding of [3H]-idazoxan to NAIBS monophasically and with very low potencies.(ABSTRACT TRUNCATED AT 250 WORDS)[4]
• Our results showed that cell incubation with tyramine (50 micromol/l) led to a time-dependent H2O2 generation which was fully inhibited by MAO A (clorgyline and RO 41-1049) and MAO B (selegiline and RO 19-6327) inhibitors [5].

Biological context of Lopac-R-107

• Ro 41-1049 produced a concentration-dependent inhibition of 3H-5-HT deamination with a Ki of 24 nM [6].

Anatomical context of Lopac-R-107

• In these studies a clear inhibition of DOPAC formation was observed with Ro 41-1049 (250 nM), while 250 nM lazabemide was found not to increase the accumulation of newly-formed DA in those tubular epithelial cells loaded with 50 microM L-DOPA [6].

Associations of Lopac-R-107 with other chemical compounds

• As previously reported for the MAO-B ligands [3H]Ro 16-6491 and [3H]Ro 19-6327, the analysis of the membrane-bound radioactivity showed that [3H]Ro 41-1049 was entirely recovered in the form of its aldehyde derivative, indicating that Ro 41-1049 was deaminated by MAO-A [3].
• In vitro binding affinities of six compounds, clorgyline, Ro 41-1049, deprenyl, fluoxetine, norfluoxetine and citalopram, were studied [7].
• Inhibition of MAO-A with 10 mg/kg Ro 41-1049 increased both parameters; inhibition of COMT with 30 mg/kg Ro 40-7592 had a similar effect [8].
• Inhibition of 5-HT (1000 microM) deamination in the rat heart by Ro 41-1049 was also a concentration-dependent process with a Ki value of 21 (16, 26) nM [9].
• The present study was aimed to determine type A and B MAO activities in rat heart and renal cortex homogenates and evaluate the sensitivity of deamination of 3H-5-HT and 14C-beta-PEA to selective MAO-A and MAO-B inhibitors, respectively Ro 41-1049 and lazabemide [9].

Gene context of Lopac-R-107

• The binding of 18F-fluoroclorgyline in the rat brain correlated with the distribution of MAO-A and was inhibited by preadministration of MAO-A inhibitors, clorgyline, and Ro 41-1049, whereas (R)-deprenyl, a MAO-B blocker, had no inhibitory effect [10].

References