Effect of MAO-B Inhibitors on Neurometabolic Profile of Patients Affected by Parkinson Disease: A Proton Magnetic Resonance Spectroscopy Study

Abstract

Parkinson’s Disease (PD) is the most common neurodegenerative movement disorder whose treatment is symptomatic. No suitable methods for assessing the effects of dopaminergic drugs on disease progression in clinical trials have yet been provided. The aim of this longitudinal study is to evaluate the influence of rasagiline and selegiline on neurometabolic profile in de novo PD patients by using Proton Magnetic Resonance Spectroscopy (1H-MRS). We enrolled de novo PD patients who were divided into two groups of 20 patients each, according to the dopaminergic treatment prescribed at the baseline visit (rasagiline or selegiline). At the baseline visit and after 12 months, all patients underwent neurological evaluation as well as 1H-MRS. Forty healthy controls (HC) underwent 1H-MRS at baseline and after 12 months. PD patients, compared to HC, showed significantly lower concentrations of NAA in the motor cortex, while the Cho levels showed a decreasing trend. After 12 months of therapy, the 1H-MRS study revealed that rasagiline and selegiline in a similar way were able to restore the NAA levels to values similar to those of HC. In addition, this neurometabolic change showed a correlation with UPDRS-III scores. This is the first longitudinal study that provides preliminary evidence that 1H-MRS may be a suitable method to evaluate objectively the influence of MAO-B inhibitors on the neurometabolic profile of PD patients. These results could open a new scenario on the hypothesis of a drug-induced slowing effect of PD progression.

5-Demethoxy-10′-ethoxyexotimarin F, a New Coumarin with MAO-B Inhibitory Potential from Murraya exotica L.

“…Although sharing 70% sequence identity, MAO-A and B displayed different substrate and inhibitor specificities; serotonin and norepinephrine are preferentially metabolized by MAO-A and phenylethylamine, benzylamine, and dopamine by MAO-B, whereas clorgyline and L-deprenyl selectively inhibit MAO-A and B, respectively. They are the well-known target for antidepressants, Parkinson’s disease, and neuroprotective drugs [ 1 , 2 , 3 , 4 ]. Monoamine oxidase inhibitors (MAOIs) were used for the treatment of various neurodegenerative disorders.…”