Defining the Role of the Monoamine Oxidase-B Inhibitors for Parkinson’s Disease

Abstract

Inhibitors of monoamine oxidase-B (MAO-B) occupy an important place in the treatment of Parkinson's disease. Selegiline was the first MAO-B to be used therapeutically, while rasagiline is a second-generation drug with higher potency and selectivity. Safinamide is an investigational MAO-B inhibitor with non-dopaminergic properties that may provide advantages over its predecessors. As a class, MAO-B inhibitors are safe and well tolerated and provide symptomatic benefit both as monotherapy and in combination with other antiparkinsonian medications from early to late stages of disease. In combination with levodopa, MAO-B inhibitors may improve motor fluctuations and allow for lower total doses of levodopa. Patient characteristics and preferences can be important factors in deciding between agents. As a class, MAO-B inhibitors have shown promise as disease-modifying agents, but the clinical trial evidence to date has not been strong enough to afford them such a label. Future research may help further elucidate their relative merits and clarify their role in altering disease progression. Key PointsRasagiline and selegiline are two monoamine oxidase-B (MAO-B) inhibitors commonly used in the treatment of Parkinson's disease (PD), while safinamide is an investigational agent of the same class.MAO-B inhibitors are safe, with few serious side effects, and provide mild but worthwhile improvements in the motor symptoms of PD, either as monotherapy or adjunctive to levodopa.The possibility that MAO-B inhibitors could slow down the progression of PD has been suggested by some studies but not by others and remains an open question.

A multiple treatment comparison meta‐analysis of monoamine oxidase type B inhibitors for Parkinson's disease

“…Robakis and Fahn discussed the role of MAO‐B inhibitors for Parkinson's disease, including selegiline, rasagline and safinamide in their review. In line with the other reviews, they concluded that MAO‐B inhibitors may be useful in the treatment of early and mild Parkinson's disease, and that they do not provide the same antiparkinsonian effect as levodopa . In a post‐hoc analysis, Hauser et al .…”

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

“…Both MAO-A and MAO-B are being discussed to provide beneficial, neuroprotective effects for PD patients (Naoi, Maruyama, Inaba-Hasegawa, & Akao, 2011;Robakis & Fahn, 2015;Kong et al, 2015). It has been demonstrated that MAO-A mediates the increased expression of genes for antiapoptotic, pro-survival Bcl-2, a subgroup of the Bcl-2 family of proteins regulating apoptosis, whereas MAO-B does not.…”

Pretreatment with potassium channel blockers of 4-aminopyridine and tetraethylammonium attenuates behavioural symptoms of Parkinsonism induced by intrastriatal injection of 6-hydroxydopamine; the role of lipid peroxidation

“…L-dihydroxyphenylalanine (L-dopa), a dopamine precursor, is a gold standard for the treatment of PD, but it has only a limited success in improving motor impairments and after some years the effect declines and patients may start to suffer from severe dyskinesias. [1][2] Recently, selegiline and rasagiline, the two selective and irreversible monoamino oxidase (MAO) inhibitors have been approved by the US FDA for the treatment of PD. It has been suggested that, these inhibitors may have neuroprotective effect and play as disease-modifying agent role in PD.…”

“…However, in compared to levodopa and dopamine agonists, MAO inhibitors at best, have the modest effect on the symptomatic relief of PD. 2 Therefore, new targets for potential pharmacological intervention should be explored and evaluated in order to slow down, delay or reverse the progress of this disease.…”

“…It has been shown that excessive K + efflux and intracellular K + depletion mediated by overactivation of voltage-gated K + channels are the key steps in apoptosis. 2,[5][6] The delayed rectifier K + channel is upregulated during certain stages of several apoptotic insults in cortical neurons, 7 myeloblastic leukaemia cells, 8 and cholinergic septal cells. 9 Also, Wang Y et al showed that K + channel blocker talatisamine attenuates beta-amyloid oligomer-induced neurotoxicity in cultured cortical neurons.…”