Rotigotine transdermal patch for the treatment of Parkinson’s Disease

Parkinson's Disease is the second most common progressive neurodegenerative disorder affecting older American adults and is predicted to increase in prevalence as the United States population ages. Resulting from a pathophysiologic loss or degeneration of dopaminergic neurons in the substantia nigra of the midbrain and the development of neuronal Lewy Bodies, idiopathic Parkinson's Disease is associated with risk factors including aging, family history, pesticide exposure and environmental chemicals (e.g., synthetic heroin use). Its ultimate cause(s) is (are) unknown. Characterized by both motor and non-motor symptoms, PD patients classically display rest tremor, rigidity, bradykinesia, and stooping posture. PD can also be associated with neurobehavioral disorders (depression, anxiety), cognitive impairment (dementia), and autonomic dysfunction (e.g., orthostasis and hyperhidrosis). Recent decades have witnessed a proliferation of medical pharmacologic therapies and innovative surgical interventions like deep brain stimulation (DBS). However, definitive disease-modifying therapy is still lacking. Experimental therapies are being developed and tested with limited results. Knowledge of strategies to promote optimal quality of life for PD patients is of paramount importance for caregivers, health providers and patients themselves.

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“…In some instances, local reactions are so severe that the drug patch must be discontinued. Most are mild to moderate in nature (30,42,43,44).…”

Section: 2non-motor Symptomsmentioning

confidence: 99%

Parkinson s disease a review

2014

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“…The past experience of late-appearing, more stable forms, as in the case of ritonavir (Chemburkar et al, 2000 ) or rotigotine (Perez-Lloret et al, 2013 ), has not only triggered the awareness of the issue of solid forms but also led to the implementation of polymorphism screenings, a survey of crystallization conditions designed to find and identify solid forms of a drug substance, as a routine in the pre-formulation phase. Experimental solid form screens may encompass up to thousands of crystallization experiments and need to be tailored to the properties of the investigated molecule (Newman, 2013 ; Cruz-Cabeza Aurora et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Supramolecular Organization of Nonstoichiometric Drug Hydrates: Dapsone

Braun

Griesser

2018

Front. Chem.

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The observed moisture- and temperature dependent transformations of the dapsone (4,4′-diaminodiphenyl sulfone, DDS) 0. 33-hydrate were correlated to its structure and the number and strength of the water-DDS intermolecular interactions. A combination of characterization techniques was used, including thermal analysis (hot-stage microscopy, differential scanning calorimetry and thermogravimetric analysis), gravimetric moisture sorption/desorption studies and variable humidity powder X-ray diffraction, along with computational modeling (crystal structure prediction and pair-wise intermolecular energy calculations). Depending on the relative humidity the hydrate contains between 0 and 0.33 molecules of water per molecule DDS. The crystal structure is retained upon dehydration indicating that DDS hydrate shows a non-stoichiometric (de)hydration behavior. Unexpectedly, the water molecules are not located in structural channels but at isolated-sites of the host framework, which is counterintuitively for a hydrate with non-stoichiometric behavior. The water-DDS interactions were estimated to be weaker than water-host interactions that are commonly observed in stoichiometric hydrates and the lattice energies of the isomorphic dehydration product (hydrate structure without water molecules) and (form III) differ only by ~1 kJ mol−1. The computational generation of hypothetical monohydrates confirms that the hydrate with the unusual DDS:water ratio of 3:1 is more stable than a feasible monohydrate structure. Overall, this study highlights that a deeper understanding of the formation of hydrates with non-stoichiometric behavior requires a multidisciplinary approach including suitable experimental and computational methods providing a firm basis for the development and manufacturing of high quality drug products.

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“…Certain mental health problems, such as depression and disturbances, including hallucinations, delusions and paranoia, are possible complications of Parkinson's disease and/or its treatment. Rotigotine (ID = 43) is for treatment in neurologic disorders and Parkinson's disease, as well as moderate-to-severe primary Restless Legs Syndrome [ 37 ]. Paliperidone (ID = 44) is the major active metabolite of risperidone.…”

Section: Resultsmentioning

confidence: 99%

Inferring drug-disease associations based on known protein complexes

Huang

et al. 2015

BMC Med Genomics

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Inferring drug-disease associations is critical in unveiling disease mechanisms, as well as discovering novel functions of available drugs, or drug repositioning. Previous work is primarily based on drug-gene-disease relationship, which throws away many important information since genes execute their functions through interacting others. To overcome this issue, we propose a novel methodology that discover the drug-disease association based on protein complexes. Firstly, the integrated heterogeneous network consisting of drugs, protein complexes, and disease are constructed, where we assign weights to the drug-disease association by using probability. Then, from the tripartite network, we get the indirect weighted relationships between drugs and diseases. The larger the weight, the higher the reliability of the correlation. We apply our method to mental disorders and hypertension, and validate the result by using comparative toxicogenomics database. Our ranked results can be directly reinforced by existing biomedical literature, suggesting that our proposed method obtains higher specificity and sensitivity. The proposed method offers new insight into drug-disease discovery. Our method is publicly available at http://1.complexdrug.sinaapp.com/Drug_Complex_Disease/Data_Download.html.

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Rotigotine transdermal patch for the treatment of Parkinson’s Disease

Cited by 24 publications

References 75 publications

Parkinson s disease a review

Parkinson s disease a review

Supramolecular Organization of Nonstoichiometric Drug Hydrates: Dapsone

Inferring drug-disease associations based on known protein complexes

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