Piribedil

Pronoran has anti-Parkinsonian effect.

Pharmacodynamics

The active substance piribedil is a dopaminergic receptor agonist. Penetrates into the bloodstream of the brain, where it binds to dopaminergic receptors in the brain, showing high affinity and selectivity for dopaminergic receptors of type D₂ and D₃. The mechanism of action of piribedil determines the basic clinical properties of the drug for the treatment of Parkinson's disease both in the initial and in the later stages of the disease with an impact on all the main motor symptoms. Piribedil, in addition to acting on dopaminergic receptors, exhibits antagonist activity of two main α-adrenergic receptors of the CNS (such as α_2A and α_2C). Synergistic action of piribedil as α antagonist₂-receptors and dopaminergic receptor agonist of the brain have been demonstrated in various animal models with Parkinson's disease: long-term use of piribedil leads to less severe dyskinesia than the use of levodopa, with similar efficacy with respect to reversible akinesia associated with Parkinson's disease.

In pharmacodynamic studies in humans, cortical electrogenesis of the dopaminergic type was shown, both on awakening and during sleep, with clinical activity in relation to various functions controlled by dopamine, this activity was demonstrated using a behavioral or psychometric scale. In healthy volunteers, piribedil has been shown to improve attention and vigilance associated with cognitive tasks.

The effectiveness of Pronoran^® as monotherapy or in combination with levodopa in the treatment of Parkinson's disease was studied in three double-blind, placebo-controlled clinical studies (2 studies compared with placebo and one compared with bromocriptine). The research involved 1103 patients of stage 1–3 on the scale of Hyun and Yar (Hoehn & jahr), 543 of which received Pronoran^®.

It is shown that Pronoran^® at a dosage of 150–300 mg / day, it is effective in acting on all motor symptoms with a 30% improvement according to a unified Parkinson's disease rating scale (UPDRS, Part III - motor) for more than 7 months with monotherapy and 12 months in combination with levodopa. Improvement of the second part of the scaleUPDRS - activity in everyday life - was evaluated in the same values.

In monotherapy, a statistically significant ratio of patients requiring emergency treatment with levodopa who received piribedil (16.6%) was less than in the group of patients who received placebo (40.2%).

The presence of dopaminergic receptors in the vessels of the lower extremities explains the vasodilating action of piribedil (increases blood flow in the vessels of the lower extremities).

Pharmacokinetics

Piribedil is rapidly and almost completely absorbed from the gastrointestinal tract and is rapidly distributed.

C_max Piribedila in plasma is achieved 3–6 hours after oral administration of a controlled release dosage form. Plasma protein binding is medium (unbound fraction is 20–30%). Due to the low binding of piribedil with plasma proteins, the risk of drug interaction when used with other drugs is low.

Piribedil plasma elimination is biphasic in nature and consists of an initial phase and a second slower phase, resulting in maintaining a stable concentration of piribedil in blood plasma for more than 24 hours.

During the combined pharmacokinetic analysis, it was shown that T_1/2 Piribedila after the on / in the introduction of an average of 12 hours and does not depend on the administered dose.

Piribedil is extensively metabolized in the liver and is excreted mainly in the urine: 75% of absorbed piribedil is excreted by the kidneys as metabolites.