Title:An Update on Nondopaminergic Treatments for Motor and Non-motor
Symptoms of Parkinson’s Disease
Volume: 21
Issue: 8
Author(s): Xiao-Zhong Jing, Xiang-Zhen Yuan, Xingguang Luo, Shu-Yun Zhang and Xiao-Ping Wang*
Affiliation:
- Department of Neurology, TongRen Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Keywords:
Parkinson’s disease, nondopaminergic treatments, nondopaminergic neurotransmitters, motor symptoms, nonmotor symptoms, update.
Abstract: Nondopaminergic neurotransmitters such as adenosine, norepinephrine, serotonin, glutamate,
and acetylcholine are all involved in Parkinson's disease (PD) and promote its symptoms.
Therefore, nondopaminergic receptors are key targets for developing novel preparations for the
management of motor and non-motor symptoms in PD, without the potential adverse events of dopamine
replacement therapy. We reviewed English-written articles and ongoing clinical trials of
nondopaminergic treatments for PD patients till 2014 to summarize the recent findings on nondopaminergic
preparations for the treatment of PD patients. The most promising research area of nondopaminergic
targets is to reduce motor complications caused by traditional dopamine replacement
therapy, including motor fluctuations and levodopa-induced dyskinesia. Istradefylline, Safinamide,
and Zonisamide were licensed for the management of motor fluctuations in PD patients, while novel
serotonergic and glutamatergic agents to improve motor fluctuations are still under research. Sustained-
release agents of Amantadine were approved for treating levodopa induced dyskinesia (LID),
and serotonin 5HT1B receptor agonist also showed clinical benefits to LID. Nondopaminergic targets
were also being explored for the treatment of non-motor symptoms of PD. Pimavanserin was approved
globally for the management of hallucinations and delusions related to PD psychosis.
Istradefylline revealed beneficial effect on daytime sleepiness, apathy, depression, and lower urinary
tract symptoms in PD subjects. Droxidopa may benefit orthostatic hypotension in PD patients.
Safinamide and Zonisamide also showed clinical efficacy on certain non-motor symptoms of PD patients.
Nondopaminergic drugs are not expected to replace dopaminergic strategies, but further development
of these drugs may lead to new approaches with positive clinical implications.
