PARKINSON'S & RASAGILINE One of the drugs that has emerged as promising and at least somewhat effective in the treatment of Parkinson's disease is known as Rasagiline. This report will explore the neurobiological and psychological implications of the drug as it relates to Parkinson's and in general. The depth and breadth of some of the studies will be discussed as well as how that evidence was found, a general discussion of Rasagiline and its current/future status as a Parkinson's treatment and how all of the above should be taken with a grain of salt given the limitations that exist. There are some great opportunities for future research when it comes to Parkinson's in general and Rasagiline in particular.

Introduction

Parkinson's is a very debilitating and difficult disorder to deal with and treat. Even with the prominence of several major celebrities (e.g. Muhammad Ali, Michael J. Fox, etc.) and increase public awareness in general, the progress on the treatment and a possible cure for Parkinson's has been frustratingly slow. Even so, progress has not been entirely missing as there are drugs like Rasagiline and other options on the market like levodopa. As different drugs and therapies have been tried, there have been some ancillary side effects and other issues. However, as the drugs and the combinations thereof become more robust and complex, the results of these therapies and pharmacological options get better. Even so, it is best to keep a good eye on the neurobiological and psychological impacts of all of the above to ensure the best quality of care and quality of life for the patient.

Method

The author of this report has consulted academic search engines to find peer-reviewed and other academic journal articles that discuss the neurobiological and psychological impacts and outcomes of people on Rasagiline as well as other Parkinson treatments. The latter will be included as a point of comparison as there should be a justification and explanation of when Rasagiline should be used, why it is used and how it tends to be or should be used. Both qualitative and quantitative data shall be used to make the points being driven home in this report. In short, any data that is valid and reliable shall be included as part of the literature review for this study and most journal articles, peer-reviewed in particular, will meet this standard. Of course, the progress and forward movement of Parkinson's treatments and the like is ever-changing so there has been an effort to keep the sources used as recent as possible unless there is a very good reason to include older information and data. Indeed, it is important at times to use the proper points of reference to drive home what is otherwise being asserted in a report like this one.

Results from Recent Studies

One of the main reasons that Rasagiline has come to be a superior option as compared other Parkinson treatments is because of the symptoms of other treatments have caused behavioral issues. One major example of this is impulse control disorders in patients that are taking drugs such as pramipexole and ropinorole. In general, it has been found that dopamine agonists like those two drugs are especially bad about this. A common manifestation of this impulse problem is hyper-sexuality. Further, there is slightly lesser evidence that there is an association between monoamine oxidase type-B inhibitors and the later onset of impulse control disorders. Conversely, Rasagiline is a second-generation MAO-B drug and it tends to induce moderate symptomatic and possibly disease modifying benefits along with good tolerability and a good safety profile in Parkinson's patients. The drug is often effective and well-tolerated when used as a solo therapy (i.e. monotherapy) but significant benefits are also seen when Rasagiline is combined with levodopa (Reyes, Kurako & Galvez-Jimenez, 2014).

When it comes to Rasagiline in particular, there have been extensive studies on how and to what degree the drug has effects on cognitive deficits in Parkinson patients that do not have dementia. Indeed, the work of Hanagasi et al. (2011) was a randomized and double-blind study that looked at this particular subject. As partially noted before, Rasagiline is a selective monoamine oxidase type-B inhibiter that works by enhancing dopaminergic transmission. This is deemed as important and vital to those that treat Parkinson's because dopamine is thought to be involved in certain cognitive processes such as a person's working memory. The Hanagasi study had patients that were receiving stable dopaminergic treatment be given Rasagiline. It was given in the amount of one milligram per day over the course of three months. Others in the group were given a placebo in the same...

Of course, this was to fetter out whether Rasagiline showed better results than not using Rasagiline. The results revealed that the people that actually received Rasagiline revealed a significant amount of improvement in digit span-backward as compared with the group taking the placebo (Hanagasi et al., 2011). Further, the overall trends of the results favored Rasagiline in digit span and digit-ordering tests. Verbal fluency scoring was also reflective of a massive scoring difference in favor of Rasagiline. Indeed, there was a huge favoring of Rasagiline when it came to semantic fluency tests. Overall, the composite cognitive domain Z scores revealed a significant difference in favor of Rasagiline compared with the placebo group in the study. There were no significant differences between the two groups in other cognitive scores, however. This would tend to indicate that while results are not great across the board when it comes to cognitive impairment improvement, there are certainly benefits to taking Rasagiline either on its own or as part of a wider pharmacological regimen for Parkinson patients (Hanagasi et al., 2011).
Because testing of drugs in humans is not always possible or without risk, a lot of drugs are tested on animals first or in concert with humans. Rasagiline, like many other drugs, has been tested on mice. When any animal ingests a drug, there is of course a breaking down of the drug into subsequent substances that are referred to as metabolites. Rasagiline is no different and one of those metabolites was studied in mice in a recent study. Indeed, the metabolite known as 1-®-aminoindan is a major metabolite of Rasagiline. It has been found that this metabolite possesses a significant amount of pharmacological benefits that are beneficial for the different cell structures and within the broader framework of animal models of neurodegeneration (Badinter, Amit, Bar-Am, Youdim & Weinreb, 2015). Badinter et al. (2015) looked at this metabolite and how it may provide for neuro-protective benefits of AI (the metabolite) on cognitive impairments and neurochemical alterations that are present in aged mice. The findings of the study indicate that following a battery of chronic and systemic treatment with the AI of aged mice led to the compound exerting a significant positive impact on the neuro-psychiatric functions and the overall cognitive behavioral deficits present in those older mice. This was proven and studied through a variety of tasks such as spatial learning, memory retention, the working memory of the mice, the learning abilities of the mice and their overall nest building behavior. Further, there was an anti-depressant-like effect when the metabolite was rendered towards the mice. Further, the AI metabolite led to a significant enhancement of neurotrophin levels. There were also increases or enhancements of brain-derived neurotrophic factor (BDNF), nerve growth factor (NFG), tyrosine kinase-B (Trk-B) receptor and synaptic plasticity markers. Examples of those markers include synapsin-1 and growth-associated protein-43 (GAP-43) in the striatum and hippocampus. (Badinter, Amit, Bar-Am, Youdim & Weinreb, 2015). The general findings of the Badinter study revealed that the AI can induce a good amount of neuroprotective effects when it comes to age-related alterations that occur against neurobehavioral functions and there is an exertion of neurotrophic up-regulatory anti-apoptotic properties in the aged animals studied (Badinter, Amit, Bar-Am, Youdim & Weinreb, 2015).

As noted in another source, Rasagiline is often used a monotherapy. This would refer to a situation where Rasagiline is the lone Parkinson's drug used. In other situations, the drug may be paired with one or more other drugs so as to provide a higher cumulative level of effect and benefit. One particular study looked at precisely such a combination. Specifically, Wu et al. (2015) looked at the combination of Rasagiline and selegiline suppress calcium from mitochondria PK11195. More simply, one can refer to this combination of Rasagiline and selegiline. The benefit of this drug combination is that there is a general protection of cell-death when the drugs are used in both cellular and animal models. Further, there is the suppression of the mitochondrial membrane permeabilization and the usual subsequent activation of what is known as the apoptosis cascade. Further, there is the induction of anti-apoptotic pro-survival genes and this obviously leads to an improvement in the general anti-apoptotic functions in cells and the body in general. Rasagiline in particular is a major catalyst for these benefits because it tends to suppress neurotoxin- and oxidative stress-induced membrane issues in isolated mitochondria. Rasagiline, when paired with…