Abstract
The motor manifestations of Parkinson's disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia.
Highlights
The cardinal manifestations of Parkinson’s disease (PD) are secondary to a degeneration of dopaminergic neurons of the substantia nigra (SN), which causes a deficiency of dopamine in the striatum [1,2,3,4,5,6,7,8,9]
The first studies with monoamine reuptake inhibitors (MAUIs) in PD were performed in the 1930s
As discussed above, the potential uses of MAUIs in PD extend way beyond depression and anxiety and, based on the data collected in this review, it may be possible to tailor the use of MAUIs with a specific profile for a particular manifestation of PD
Summary
The cardinal manifestations of Parkinson’s disease (PD) are secondary to a degeneration of dopaminergic neurons of the substantia nigra (SN), which causes a deficiency of dopamine in the striatum [1,2,3,4,5,6,7,8,9]. With increasing duration of LDOPA therapy, a range of motor and nonmotor complications, encompassing dyskinesia, wearing-off, and psychiatric manifestations, develop [18, 19] Because they can increase the levels of monoamine in the synaptic cleft by inhibiting the action of the monoamine transporters, monoamine reuptake inhibitors (MAUIs) represent potential agents in the therapy of PD. As will be discussed in this review article, their uses extend beyond the motor symptoms of the disease Several of these compounds, with different affinities and pharmacological profiles, have been tested in animal models of PD and idiopathic PD. The aim of this review is to provide an overview of the effects of MAUIs against different symptoms of PD and to establish what the optimal monoamine reuptake profile might be in order to target specific manifestations of the disease, either as monotherapy or as an adjunct to L-DOPA therapy
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