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Advanced Neurology Piribedil for Parkinson’s disease

different mechanisms. They decrease DA turnover and kinetics and is composed of a first phase characterized by a
free radical generation in the substantia nigra, and possess half-life of 1.7 h and a second, slower phase characterized
antioxidant properties. Pathological conditions were by a half-life of 6.9 h [12,30] . A sustained-release formulation
reversed by piribedil in a dose-dependent manner, which has a half-life of up to 21 h once steady state is attained,
showed to increase the expression of lactate dehydrogenase which is longer than levodopa and multiple DR agonist-
and reduce the expression of tyrosine hydroxylase positive/ like pramipexole (8 – 12 h) and ropinirole (6 – 8 h) [30,31] .
total neurons ratio after infusion . The mechanisms and According to Chinese Guidelines for the Treatment of
[29]
th
pharmacokinetics of non-ergot DR agonists are shown PD (4 Edition), piribedil sustained-release tablets can
in Table 1 . In 1969, piribedil was marketed as the first be split in half in special cases to reduce the side effects.
[12]
non-ergot partial DA D2/D3-selective agonist. Piribedil Continuous dopaminergic stimulation of DA receptors
1-(2-pyrimidyl)-4 piperonyl piperazine is a non-catechol will delay the motor complications. Piribedil has a longer
analog of DA . half-life than that of levodopa. It stimulates DA in a
[29]
less pulsatile manner and avoids adverse effects due to
Mechanisms of piribedil include the following: DR-pulsed stimulations [12,32,33] .
i. Acting as signal-specific partial agonists at D2/D3
receptors. Partial agonism is sufficient to improve motor 3. Clinical applications of piribedil in the
dysfunction in PD. While improving motor dysfunction, treatment of PD
the avoidance of potentially excessive stimulation of D2/
D3 receptors may reduce the incidence of complications, The goal of PD treatment is to effectively improve patients’
such as cognitive dysfunction and abnormal prolactin motor and non-motor symptoms, prevent complications,
[15]
excretion. The combined stimulation of D1 and D2 and improve patient’s workability and quality of life . The
receptors can increase the anti-PD effect and reduce the International Parkinson and Movement Disorder Society
intensity of dyskinesia . considered piribedil efficacious and clinically useful for the
[17]
[29]
ii. α2-adrenoreceptor antagonistic effects. Piribedil blocks treatment of PD .
the α2-adrenoreceptor and reinforces dopaminergic, A meta-analysis only involving randomized controlled
adrenergic, and cholinergic transmission. This effect trial (RCTss) showed that the combination of piribedil
may decrease the incidence of dyskinesia, improve the and levodopa is more effective compared with levodopa
motor function and cognition, elevate the mood, and monotherapy (mostly focused on motor symptoms and
reduce the risk of daytime somnolence . few on mood) without significant worsening of drug-
[30]
iii. Low affinity to multi-subtype 5-HT receptors. Piribedil related adverse reactions that include gastrointestinal tract
may decrease serotonergic 5-HT1-related and 5-HT2- reactions and neuropsychiatric disorders . Although this
[34]
related side effects, such as valvular heart diseases . meta-analysis on RCTs revealed that the combination of
[17]
iv. Minimal interaction with histaminergic and piribedil and levodopa did not significantly increase the
cholinergic receptors . drug-related adverse reactions of patients with PD, these
[12]
adverse reactions can still happen in clinical practice.
2.2. Pharmacokinetics
Piribedil is used as an oral medication. It reaches 3.1. Motor symptoms
maximum concentration 1 hour after single oral dose Piribedil can improve motor symptoms in patients with
with rapid absorption. Oral bioavailability is low due to PD by increasing DR excitability . In early untreated or
[34]
an extensive first-pass metabolism. Hepatic metabolism levodopa-treated non-fluctuating PD patients, piribedil
produces many metabolites, which are excreted through has shown superiority to placebo (level 1 evidence) for
kidney. The elimination of piribedil follows biphasic the alleviation of all cardinal motor symptoms. The typical

Table 1. Mechanisms and pharmacokinetics of non‑ergot DR agonists
Parameters Piribedil Pramipexole IR Ropinirole IR Rotigotine transdermal patches
DR effects D D D >D D D >D D D D D >D D
2, 3 3 2, 4 2 3, 4 1, 2, 3 4, 5
Half-life (h) 1.7 – 6.9 8 – 12 6 5 – 7
Dose (mg/day) 150 – 250 1.5 – 4 8 – 24 8 – 16
Excretion pathway 68% through kidneys; 90% through kidneys 88% through kidneys 71% through kidneys; 23%
25% through bile through small intestine
DR: Dopamine receptor; IR: Immediate-release

Volume 2 Issue 1 (2023) 3 https://doi.org/10.36922/an.290