Trivastal (piribedil) / Servier - LARVOL DELTA

Dopamine receptors: Potential therapeutic targets for ischemia-reperfusion injury: A review. (PubMed, Int J Biol Macromol) - "Compounds with high binding affinity, effectiveness and safety, such as piribedil, tadalafil, salvianolic acid A, PD168077, and bromocriptine, have emerged as promising candidates for clinical translation. Concurrently, cutting-edge methods like artificial intelligence offer new perspectives and tools for rational design of drugs targeting these receptors for I/R injury treatment. In-depth exploration of dopamine receptors provides a critical entry point for elucidating the complex pathophysiological mechanisms of I/R injury, while also laying a solid theoretical foundation for development of novel and effective therapeutic strategies."

Journal • Review • Cardiovascular • Reperfusion Injury

Modulation of AMPK/SIRT1 signaling by piribedil attenuates cyclophosphamide-induced nephrotoxicity via PI3K/Akt, MAPKs, and TLR4/NLRP3 pathways with regulation of KIM-1/NGAL. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Piribedil effectively protects against CP-induced nephrotoxicity by modulating AMPK/SIRT1 and related oxidative and inflammatory pathways, supporting its potential use in drug-induced kidney injury."

IO biomarker • Journal • Nephrology • Oncology • Renal Disease • HMOX1 • IL1B • IL6 • KIM1 • LCN2 • NLRP3 • TLR4 • TNFA

Catecholaminergic storm and extreme blood pressure lability induced by combined levodopa/benserazide, selegiline, and piribedil in Parkinson's disease: a case report. (PubMed, Neurol Sci) - "This case demonstrated that combined dopaminergic therapy could induce catecholamine storm via synergistic effects, leading to life-threatening fluctuations in BP. Timely identification and adjustment of treatment regimens could effectively reverse cardiovascular risk. However, it was crucial to carefully consider the balance between the progression of motor symptoms and changes in medication treatment."

Journal • Cardiovascular • CNS Disorders • Fatigue • Movement Disorders • Parkinson's Disease

Rapid health technology assessment of six non-ergot dopamine-receptor agonists for the treatment of early Parkinson's disease. (PubMed, Front Pharmacol) - "The composite scores of the six NEDAs are presented as follows: 74.99 points for pramipexole ER, 74.90 points for piribedil, 72.40 points for pramipexole IR, 70.78 points for rotigotine patch, 69.06 points for ropinirole PR and 68.41 points for ropinirole IR. Based on our comprehensive multi-criteria assessment, pramipexole ER, pramipexole IR, rotigotine patch, and piribedil are strongly recommended for inclusion in the formularies of medical institutions as therapeutic options for patients with early PD."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Psychiatric Comorbidities in Parkinson's Disease: A Moroccan Perspective on Anxiety and Depression. (PubMed, Diseases) - "L-DOPA alone was used to treat half of the patients, while combinations of Trivastal, Sifrol, anticholinergics, or antidepressants were given to the other half. Regardless of the method of treatment or stage of the disease, psychiatric symptoms are prevalent. For PD patients to benefit from early interventions and achieve an improved quality of life, routine screening is crucial."

Journal • CNS Disorders • Depression • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Remarkable therapeutic effects of methylphenidate in periodic limb movement disorder comorbid with excessive daytime sleepiness: a case report. (PubMed, Front Neurosci) - "Initially, we used levodopa 250 mg per night for 12 weeks, then piribedil 50 mg per night was arranged as the second drug for 12 weeks, and the third drug, pramipexole, was prescribed at a dosage of 0.25 mg per night for 12 weeks, but the EDS was persistent despite the periodic leg movement index (PLMI) returning to normal. A 2.5-year follow-up was scheduled for taking methylphenidate; the symptoms of EDS were steadily well controlled, and PLMI was still kept in the normal range. This finding suggests that methylphenidate is an optimal therapeutic approach for the management of PLMD comorbid EDS."

Journal • Excessive Daytime Sleepiness • Movement Disorders • Sleep Disorder

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination. (PubMed, Beilstein J Org Chem) - "The remedy for Parkinson's disease, piribedil, was obtained in high yield. The plausible mechanism of the elaborated process was proposed and supported by DFT calculations."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Hydrophilic and Amphiphilic Macromolecules as Modulators of the Physical Stability and Bioavailability of Piribedil: A Study on Binary Mixtures and Micellar Systems. (PubMed, Mol Pharm) - "Moreover, an improvement in the bioavailability of the API contained in all tested formulations (binary and micellar systems) was observed, with PBD-starPVP micelles exhibiting the most desirable drug release profile within the polymer matrix, as well as the highest concentration of released drug. The obtained data highlight the crucial role of the type and topology/architecture of the polymer in the design of novel pharmaceutical formulations."

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Multigenetic pharmacogenomics-guided treatment shows greater improvements on motor symptoms compared to usual therapy in Parkinson's disease: a small real-word prospective cohort study. (PubMed, Front Pharmacol) - "These differences remained significant after adjusting for increases in levodopa equivalent daily dose (p = 0.011 and p = 0.002, respectively) and piribedil use (p = 0.006 and p = 0.004, respectively)...Additionally, we identified several SNPs associated with the responsiveness to chronic administration of multiple anti-parkinsonian drugs. However, to confirm these findings, well-designed studies with larger, well-characterized samples are necessary."

Biomarker • Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Integration of Metabolomics and 16S Ribosomal RNA Sequencing to Elucidate the Pathogenesis of Ankylosing Spondylitis. (PubMed, Immun Inflamm Dis) - "A disrupted gut microbiota and altered metabolites are present in AS patients. Integrating microbiome and metabolomic data reveals significant disruptions in AS patients, improving our understanding of its pathogenesis."

Journal • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies

Piribedil and thymol mitigate vancomycin-evoked nephrotoxicity in rats through modulation of Keap-1/Nrf2/HO-1 and NF-κB/Bax/caspase 3 signalings. (PubMed, Drug Chem Toxicol) - "In addition, NF-kB, Bax, and caspase 3 expression levels were considerably declined after piribedil or thymol co-treatment. These findings revealed that co-administration of piribedil or thymol with VAN may be a sensible therapeutic approach for reducing renal intoxication caused by VAN."

Journal • Preclinical • Oncology • BAX • CASP3 • CST3 • IL1B • KEAP1 • KIM1 • MPO • NFKB1 • TNFA

Neurochemical mechanisms of tremor in Parkinson's disease (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "It is discusses how changes in neurotransmitter systems may influence the clinical diversity of tremor and differences in response to therapy. Data from clinical trials demonstrating the effect of the dopamine receptor agonist piribedil on tremor are presented."

Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

Catalytic Reductive Amination and Tandem Amination-Alkylation of Esters Enabled by a Cationic Iridium Complex. (PubMed, Angew Chem Int Ed Engl) - "The method is highly chemoselective and tolerates a variety of functional groups such as bromo, trifluoromethyl, ester, and cyano groups. The value of the method was demonstrated by the one-step catalytic synthesis of two bio-relevant N-mono-methyl α-amino esters and the antiparkinsonian agent piribedil, as well as by the use of two shorter chain triglycerides as alkylating feedstock."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Sex differences of fall-risk-increasing drugs in the middle-aged and elderly: a descriptive, cross-sectional study of FDA adverse event reporting system. (PubMed, Sci Rep) - "For males, the top 3 signals with the highest ROR were fluprednidene acetate, potassium hydroxide, ketazolam (ROR: 216.86, 108.43, 108.43), while the top 3 signals with the highest IC025 were clomethiazole, piribedil, melperone (IC025: 3.31, 3.24, 2.99). We offered a series of FRIDs and suggested their sex differences in falls through the FAERS. In the future, it is essential to balance the inclusion of women and men, and analyse sex-stratified for FRIDs."

Adverse events • Journal • Observational data • Retrospective data • Cardiovascular • Musculoskeletal Diseases

A novel arylpiperazine derivative (LQFM181) protects against neurotoxicity induced by 3- nitropropionic acid in in vitro and in vivo models. (PubMed, Chem Biol Interact) - "In the pursuit of novel antioxidant therapies for the prevention and treatment of neurodegenerative diseases, three new arylpiperazine derivatives (LQFM181, LQFM276, and LQFM277) were synthesized through a molecular hybridization approach involving piribedil and butylated hydroxytoluene lead compounds...Interestingly, using the same in vivo model, LQFM181 also reduced locomotor behavior and memory dysfunction through its ability to decrease cholinesterase activity. Consequently, LQFM181 emerges as a promising candidate for further investigation into its neuroprotective potential, positioning it as a new therapeutic agent for neuroprotection."

Journal • Preclinical • CNS Disorders • CAT

Prescription patterns in treatment of Parkinson's disease in tertiary centers in Poland (CONy 2024) - "465 patients were treated with LD (mean dose 810.58mg), 292 with DA (ropinirole – 176 (mean dose 8.64mg), pramipexole – 105 (mean dose 1.76mg), piribedil - 8, rotigotine - 3), 202 with MAO-B inhibitors (rasagiline 198, selegiline 4), 197 with amantadine, 7 with entacapone and 4 with anticholinergics. Patients were divided into subgroups depending on their HY score, age and duration of the disease, then pharmacotherapy of each group was analyzed showing that in every group levodopa was most often prescribed drug and remains a gold standard in treatment of PD in tertiary centers in Poland. Dopamine agonists were the second most frequently prescribed group of medications in our study, although they were less frequently used in older population (70 years old) and with HY score of 3 or more."

CNS Disorders • Movement Disorders • Parkinson's Disease

Postural stability and walking in Parkinson's disease (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "The article discusses the existing problems according to the latest literature data, a review on the treatment and rehabilitation of postural instability. Special attention in the article is paid to dopamine receptor agonists - namely, piribedil, prescribed for the correction of these disorders."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Comparison of the effectiveness, safety, and costs of anti-Parkinson drugs: A multiple-center retrospective study. (PubMed, CNS Neurosci Ther) - "Carbidopa/levodopa or levodopa/benserazide might exhibit better clinical improvement with less medical cost, while piribedil presented less clinical improvement but a higher risk of headache/dizziness, gastrointestinal, and neuropsychiatric symptoms."

Journal • Retrospective data • CNS Disorders • Gastrointestinal Disorder • Movement Disorders • Pain • Parkinson's Disease • Psychiatry

A Systematic Review of Pharmacological Interventions for Apathy in Aging Neurocognitive Disorders. (PubMed, Brain Sci) - "Pharmacological interventions for apathy in aging neurocognitive disorders are complex and under-investigated. The continuation of systematic research efforts and the provision of individualized treatment for patients suffering from these disorders is vital."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Frontotemporal Lobar Degeneration • Huntington's Disease • Movement Disorders • Parkinson's Disease • Psychiatry

Stereoselective synthesis of C-substituted piperazines mediated by an iridium catalyst (ACS-Fall 2023) - "Piperazine is considered a privileged scaffold in medicinal chemistry,[1] which has been used in a vast number of drugs across different areas, such as indinavir for HIV treatment, imatinib for chemotherapy, and piribedil for antiparkinsonian treatment. However, their synthesis is often accompanied by stereoselectivity problems and, in some cases, challenging multi-step synthetic processes. Therefore, selective, atom-economical methods for forming C-substituted piperazines from easily synthesized precursors, which can be modified to obtain a range of different piperazines, are highly desirable.[2] Recent research has shown significant progress in this area, such as the synthesis of C-substituted piperazines starting from imines containing aromatic substituents using an aluminum complex, as reported by Mendoza et al.[3]Herein, we report a stereoselective catalytic method for synthesizing C-substituted piperazines from imines with both aromatic and aliphatic substituents,..."

CNS Disorders • Human Immunodeficiency Virus • Infectious Disease • Movement Disorders • Parkinson's Disease

Comparative efficacy and safety of six non-ergot dopamine-receptor agonists in early Parkinson's disease: a systematic review and network meta-analysis. (PubMed, Front Neurol) - "Novel long-acting formulations of NEDAs including pramipexole extended-release (ER), ropinirole prolonged-release (PR), and rotigotine transdermal patch have been developed. In addition, the incidence of adverse reaction of ropinirole IR was relatively high (nausea: 0.678; somnolence: 0.752; dizziness: 0.758; fatigue: 0.890). In this systematic review and network meta-analysis of six NEDAs, piribedil exhibited better efficacy, especially as monotherapy, and ropinirole IR was associated with a higher incidence of adverse events in patients with early PD."

Retrospective data • Review • CNS Disorders • Fatigue • Movement Disorders • Parkinson's Disease

Motor and autonomic disorders influence on pain syndrome of patients with Parkinson's disease of the I-III H&Y stages (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "The piribedil inclusion contributes to the reduction of pain syndrome, regardless is it used in monotherapy or in conjunction with levodopa preparations."

Journal • CNS Disorders • Constipation • Depression • Gastroenterology • Gastrointestinal Disorder • Mood Disorders • Movement Disorders • Musculoskeletal Pain • Otorhinolaryngology • Pain • Parkinson's Disease • Psychiatry

Social behavioral profiling by unsupervised deep learning reveals a stimulative effect of dopamine D3 agonists on zebrafish sociality. (PubMed, Cell Rep Methods) - "The D3 agonists pramipexole, piribedil, and 7-hydroxy-DPAT-HBr rescued social deficits in a valproic-acid-induced zebrafish autism model. The ZeChat platform provides a promising approach for dissecting the pharmacology of social behavior and discovering novel social-modulatory compounds."

Journal • Autism Spectrum Disorder • Genetic Disorders

Upper gastrointestinal tract dysfunction and its correction by dopamine agonists for patients with Parkinson's disease of I-III stage (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "The inclusion of piribedil (150-250 mg/day) in the 6-months therapy reduces the dysfunction of the upper gastrointestinal tract (by 61 and 74% of the initial level of dysphagia and sialorrhea, respectively) regardless the drug use in monotherapy or in complex therapy with levodopa."

Journal • Anorexia • CNS Disorders • Gastrointestinal Disorder • Movement Disorders • Otorhinolaryngology • Parkinson's Disease

A General C-N Cross-Coupling to Synthesize Heteroaryl Amines Using a Palladacyclic N-Heterocyclic Carbene Precatalyst. (PubMed, Org Lett) - "Applying this precatalyst enabled a general protocol for Pd-catalyzed C-N cross-coupling reactions of challenging five- or six-membered ring heteroaryl chlorides and various heterocyclic amines. The desired aminated products, including commercial pharmaceuticals or key intermediates such as piribedil, cyprodinil, BRAF inhibitor, tripelennamine, 517-β-hydroxysteroid dehydrogenase inhibitor, brexpiprazole, and sonidegib, were achieved in good to excellent yields (>61 examples, ≤99% yields)."

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