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Advanced Neurologyurology
Advanced Ne Piribedil for Parkinson’s disease

65 years by 2050. This will result in an expansion of aging cell bodies in the substantia nigra pars compacta
population , which might further increase the incidence (SNc) and dysfunction of neurons, which produces
[4]
of PD in China. It is expected that by 2030, China will dopamine (DA) . It is commonly regarded that the
[17]
contribute to over half of the world’s PD patients . The death of dopaminergic neurons in SNc is influenced
[5]
global burden of PD has been doubled as the age and life by DA metabolism, oxidative stress and mitochondrial
expectancy of the population increases. PD resulted in dysfunction, endoplasmic reticulum stress, impaired
approximately 3.2 million disability-adjusted life years and protein degradation mechanisms, and neuroinflammation.
caused >210,000 deaths worldwide . Dopaminergic neurons are susceptible to mitochondrial
[6]
Motor symptoms such as akinesia and bradykinesia, oxidative stress induced by DA oxidation. Mitochondrial
tremor, and rigidity , and non motor symptoms such as oxidative stress leads to an accumulation of oxidized
[7]
depression, fatigue, altered gait, psychosis, apathy, sleep DA that suppresses the activity of glucocerebrosidase,
disorders, and sensory abnormalities [8,9] affect the patient and lysosomal dysfunction, and α-synuclein accumulation in
[18,19]
caregiver’s quality of life. Thus, PD causes heavy economic PD neurons . The accumulation of DA in cytoplasm
burden to families and society [10,11] . Levodopa, dopamine is neurotoxic, resulting in selective death of neurons in
[20]
receptor agonists (DRA), monoamine oxidase B inhibitors, SNc . Endoplasmic reticulum stress also causes neuronal
catechol-O-methyltransferase inhibitors, anticholinergic death, which is caused by the accumulation of misfolded
agent, and amantadine are the most common first-line or unfolded proteins [21,22] . In addition, PD pathology
therapy for PD. In patients with chronic PD, the long-term affects autophagy, and stimulation of autophagic activities
use of levodopa would result in decreased response to the may be a compensatory mechanism induced by persistent
drug, dose adjustments, and frequent emergence of motor reticulum stress. Impairment of autophagy tends to
complications. DRA have multiple advantages, such as accumulate abnormal α-synuclein in the Lewy bodies
direct dopamine receptor (DR) agonistic effect, long half- which subsequently causes parkinsonism [23,24] .
life, and antidepressant effect. No evidence of oxidative DA binds to G-protein coupled receptors or DA
metabolism and interactions with food amino acids with receptors. These receptors can be classified as D1-like
DR agonists was observed. Daytime somnolence and receptors (D1 and D5) and D2-like receptors (D2, D3,
behavioral changes are some of its drawbacks. DR agonists D4). These receptors mediate all physiological functions
have been increasingly recognized in the treatment of PD, of catecholaminergic neurotransmitter, DA. D4 and D5
of which non-ergot DR agonists are highly recommended receptors may have limited effects on motor or cognition
because of their less adverse effects . function [25,26] . DR agonists can stimulate DR to produce
[12]
Non-ergot DR agonists were approved as the first-line dopaminergic-like effects, thus improving motor and
medications for the treatment of PD according to multiple non-motor symptoms. D2 and D3 receptors are the DRs
national and international authoritative guidelines. mainly related to PD. Stimulating the D2 receptors can
Piribedil has been used as the first non-ergot DR agonist improve motor function and cognitive functions, such
in China. Piribedil improves patient’s motor and non- as learning and memory, through prefrontal cortical
motor symptoms, and prevents motor complications in an regulation. D3 receptors can slightly regulate cognitive
advanced stage of PD with minimal adverse reactions such functions through hippocampal and play a key role in
as somnolence [12-16] . reward and reinforcement mechanisms. Evidence shows
that D1 receptors might be related to motor function.
However, there is no standardized guideline for the use Piribedil is a D2-like agonist but the D1 agonist (S584) is
of piribedil in PD. Based on the evidence-based medical one of its metabolites . Relevance of D1 agonistic activity
[27]
research and domestic practical experience, experts put remains speculative but it is thought to have consequences
together comprehensive and reliable instructions on regarding efficacy and tolerability of piribedil. A combined
piribedil administration for clinicians. In this review stimulation of D1 and D2 receptors in animal model
article, we highlight the pharmacological properties of potentiates antiparkinsonian responses of piribedil and
piribedil and its clinical applications in PD, management participates in the pathophysiology of dyskinesia .
[28]
of adverse events and drug interactions.
DRA acts as adjuncts to levodopa. DAs can be divided
2. Pharmacological properties of piribedil into ergot derivatives and non-ergot derivatives. Piribedil,
pramipexole, apomorphine, ropinirole, and rotigotine are
2.1. Pharmacological mechanism the common non-ergot DR agonists. These will bind to
Clinical manifestations of patients with PD are mainly DA D2-like family of DA receptors [12,17] . Neuroprotection
characterized by the degeneration of nigral dopaminergic conferred by DA agonists is thought to be provided by

Volume 2 Issue 1 (2023) 2 https://doi.org/10.36922/an.290