Introduction
The clinical syndrome of Parkinsonism is most frequently caused by Parkinson’s disease (PD). These two conditions share many symptoms, and, as a result, the proposed treatment methods are similar in both illnesses. Since the cases of Parkinsonism symptoms development as a result of using some medications are numerous, scientists are constantly working on the improvement of the techniques employed in the treatment of Parkinsonism and Parkinson’s disease. Numerous experiments are being performed to check the validity of drugs proposed to relieve the symptoms of the two conditions. Future management modalities involve clinical trials, new medicines, and original therapeutic approaches.
Experimental and Future Clinical Options for PD Treatment
The most common pharmacotherapy options for PD treatment are L-DOPA, monoamine oxidase, amantadine, and dopamine agonists. However, with the disease’s progress, these options become insufficient, and their side effects begin to show. To improve the existing treatment methods, researchers are constantly working on finding out new drugs and clinical modalities that would decrease the progress of Parkinsonism and PD. While the application of creatine monohydrate, coenzyme Q10, pioglitazone, and other drugs has not brought positive results, current clinical trials are aimed at investigating the outcomes of the application of other medicine. Among the new options are isradipine, nicotine, inosine, caffeine, and immunization against α-synuclein.1 Other treatment options incorporate gene therapy and treatment addressing non-dopaminergic systems.2
Adenosine A2A Antagonists as a Promising Drug Category
Since neurotransmitters are partially responsible for Parkinson’s disease’s symptomatology, perspectives of future research include the development of non-dopaminergic PD therapies. Out of all the current drug categories, researchers consider adenosine A2A antagonists as a highly prospective solution.3 Adenosine A2A antagonists’ positive anti-parkinsonian reaction has allowed proposing a rationale for clinical trials which will assess the safety and therapeutic capacity of these antagonists in the PD patients. Modern pharmacological attempts connected with the potential application of A2A antagonists in PD therapy are concentrated on examination of vipadenant and preladenant, modern derivatives in drugs’ development such as SYN115, and a comparatively old drug istradefylline which has recently been approved in Japan as an anti-parkinsonian drug.3
The benefits of the A2A receptor blockade have been proven in several experimental models. Experiments demonstrated that a combined treatment by A2A antagonist and L-DOPA eliminated the wearing-off generated by L-DOPA without declining dyskinesia. Additionally, a low L-DOPA dose led to motor symptoms improvement with less dyskinesia.3 Despite their positive impact on the disease, adenosine A2A antagonists may present some side effects on the patients. These effects include lowered blood pressure, vomiting, and nausea. The application of the drug for a long time may cause a decrease in its efficiency and disease advancement.
Preladenant
Experimental application of preladenant showed a mean reduction in OFF time and an insignificant increase in ON time. The future study involves the evaluation of preladenant’s impact on nonmotor symptoms.4
Istradefylline
This drug has a mild effect in OFF time reduction and is well tolerated. However, it does not have a meaningful potency as a monotherapy method. Thus, the future of this drug is under question.4
SYN115
A double-blind placebo-controlled study was performed in which the patients were treated with SYN115 and were assessed before and during an infusion of levodopa. The experiment showed that the tapping speed was faster with SYN115 than with a placebo. Future research will be concerned with a phase 2 trial in patients who have motor fluctuations.4
Levodopa Formulations
Levodopa/Carbidopa Intestinal Gel (LCIG)
LCIG infusion is considered to be a highly productive method of motor fluctuations treatment. The main disadvantages are the procedure’s invasiveness, the difficulties of device malfunction management, and the discomfort of carrying the pump. Future research presupposes a phase 3 randomized study aimed at comparing LCIG with oral levodopa/carbidopa.4
IPX066
IPX066 proved to sustain levodopa concentrations for a much longer time than carbidopa/levodopa IR. Patients with motor fluctuations can probably be converted to IPX066 TID and observe a reduction in the OFF time. Future trials are needed to find out whether dyskinesia development can be reduced by continuous dopamine stimulation.4
Other Perspective Antiparkinsonian Drugs
XP21279
This drug proved to provide sustained levodopa blood concentrations. Further experiments are necessary to find out its full potential.
ND0611
ND0611 is a carbidopa solution which is administered by a patch. In preclinical experiments, this drug proved to increase levodopa concentrations. Future research will show whether it is capable of improving levodopa pharmacokinetics.4
Safinamide
The advantage of safinamide is its possibility to release of inhibition of glutamate and MAO-B inhibition. Further studies will investigate the drug’s potency to provide antidyskinetic outcomes.4
Cogane (PMY50028)
Cogane is an inducer of the oral neurotrophic factor. Experiments showed that it could reverse and reduce cell loss and neuronal atrophy. Future studies are aimed at identifying the dose range for the drug.4
Conclusion
Parkinsonism and Parkinson’s disease are among the most severe illnesses affecting people. Existing drugs and treatment options can partially relieve the symptoms people are experiencing. However, profound research is necessary to find better ways of a cure for these conditions. Current studies and future study plans involve discovering new drug types, performing clinical trials, and coming up with new therapeutic approaches. By fulfilling these plans, the researchers will provide enhanced life conditions for many people suffering from the mentioned serious disorders and their complications.
References
Oertel W, Schulz JB. Current and experimental treatments of Parkinson disease: a guide for neuroscientists. J Neurochem. 2016;139:325-337.
Cenci MA, Ohlin KE, Odin P. Current options and future possibilities for the treatment of dyskinesia and motor fluctuations in Parkinson’s disease. CNS & Neurol Disord – Drug Targets. 2011;10:670-684.
Pinna A. Adenosine A2A receptor antagonists in Parkinson’s disease: progress in clinical trials from the newly approved Istradefylline to drugs in early development and those already discontinued. CNS Drugs. 2014;28(5):455-474.
Hauser RA. Future treatments for Parkinson’s disease: surfing the PD pipeline. Int J Neurosci. 2011;121:53-62.