Parkinson's disease (PD) is a progressive neurological ailment with a slower rate of advancement that is more common in older adults. The biggest risk factor for PD is getting older, and those over 60 have an exponentially higher incidence of this condition. The failure of the mitochondrial electron chain, changes in the dynamics of the mitochondria, and abnormalities in calcium and ion homeostasis are all symptoms of Parkinson's disease (PD). Increased mitochondrial reactive oxygen species (mROS) and an energy deficit are linked to these alterations. Levodopa (L-DOPA) is a medication that is typically used to treat most PD patients, but because of its negative effects, additional medications have been created utilizing L-DOPA as the parent molecule. Ergot and non-ergot derivatives make up most PD medications. PD is successfully managed with the use of dopamine agonists (DA). To get around the motor issues produced by L-DOPA, these dopamine derivatives can directly excite DA receptors in the postsynaptic membrane. In the past 10 years, two non-ergoline DA with strong binding properties for the dopamine D2 receptor (D2R) and a preference for the dopamine D3 receptor (D3R) subtype, ropinirole, and pramipexole (PPx) have been developed for the treatment of PD. This review covers the most recent research on the efficacy and safety of non-ergot drugs like ropinirole and PPx as supplementary therapy to DOPA for the treatment of PD.

Impurities compounds in any pharmaceutical product or drug substance are inevitable from a chemistry point of view. The quality and safety of a pharmaceutical product are also significantly affected by these impurities content; therefore, impurities need to be identified and characterized through the use of appropriate analytical methods. Pramipexole is a nonergot dopamine agonist used to treat various Parkinson's disease symptoms. Two unknown impurities were detected from a pramipexole dihydrochloride solid dosage form. These impurities were identified and characterized using ultra-performance liquid chromatography coupled with high-resolution mass spectroscopy (UPLC-HRMS). These impurities were found to be enriched when mannitol existed in the formulation. The structure and mechanism involved in the existence of the impurities were proposed. Furthermore, observation of the binding affinity potential risk of these impurities to the pramipexole receptor has also been demonstrated through molecular docking and molecular dynamics simulation study. The binding energy result showed that pramipexole interaction with dopamine receptors D2 and D3 was higher than pramipexole mannose adduct and pramipexole ribose adduct.

Parkinson's disease (PD) affects around ten million people worldwide and is considered the second most prevalent neurodegenerative disease after Alzheimer's disease. In addition, there is a higher risk incidence in the elderly population. The main PD hallmarks include the loss of dopaminergic neurons and the development of Lewy bodies. Unfortunately, motor symptoms only start to appear when around 50-70% of dopaminergic neurons have already been lost. This particularly poses a huge challenge for early diagnosis and therapeutic effectiveness. Actually, pharmaceutical therapy is able to relief motor symptoms, but as the disease progresses motor complications and severe side-effects start to appear. In this review, we explore the research conducted so far in order to repurpose drugs for PD with the use of nanodelivery systems, alternative administration routes, and nanotheranostics. Overall, studies have demonstrated great potential for these nanosystems to target the brain, improve drug pharmacokinetic profile, and decrease side-effects.

Prolonged administration of l-3,4-dihydroxyphenylalanine (l-DOPA) for Parkinson's disease (PD) is hampered by motor complications related to the progressive incapacity of residual nigrostriatal neurons to properly utilize the drug. Direct stimulation of dopaminergic (DAergic) receptors with specific compounds (DA agonists) has, therefore, become an additional therapeutic tool for PD.

DA agonists have considerable anti-parkinsonian symptomatic efficacy, although they are less potent than l-DOPA. This review summarizes pre-clinical and clinical data on DA agonists and their role in treating PD. Specific focus was put on second-generation, first-line non-ergolinic DA agonists and their motor, non-motor and putative neuroprotective effects. The anti-parkinsonian potential of recently developed DA agonists that reached Phase II and III clinical trials was also addressed.

DA agonists can be useful along the whole natural course of PD, as monotherapy in the initial phase or combined with l-DOPA in advanced PD. Extended-release formulations have been developed for second-generation DA agonists, which are better appreciated by patients. Neuroprotective properties have been proposed for DA agonists, based on pre-clinical studies, but never convincingly demonstrated in patients. New DA agonists, with better symptomatic efficacy and devoid of the side effects that characterize current compounds, are needed.