Plasma measurements of levodopa and its major metabolites including dopamine and 3-O-methyldopa have been limited by cumbersome methods and poor sensitivity within relatively narrow ranges of plasma levels. We now report a modification of an HPLC method that permits concomitant measurements of a wide range of concentrations of levodopa, dopamine (DA), carbidopa, 3-O-methyldopa (3-OMD) and 3,4-dihydroxyphenyl acetic acid (DOPAC) from one HPLC injection. The recoveries ranged from 77 to 107% with an intra-day precision around 5% (CV) and inter-day CV's about 10-20%. This validated method will simplify pharmacokinetic studies of levodopa and its metabolites for mechanistic studies or therapeutic clinical monitoring which play a crucial role in development of strategies to prolong motor benefits from individual doses and reduce involuntary movements called dykinesias.
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http://dx.doi.org/10.1016/j.jchromb.2006.03.027 | DOI Listing |
Int Immunopharmacol
January 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University- Arish Branch, Arish 45511, Egypt.
Unlabelled: Despite a deep understanding of Parkinson's disease (PD) and levodopa-induced dyskinesia (LID) pathogenesis, current therapies are insufficient to effectively manage the progressive nature of PD or halt LID. Growing hypotheses suggested the NOD-like receptor 3 (NLRP3) inflammasome and orphan nuclear receptor-related 1 (Nurr1)/glycogen synthase kinase-3β (GSK-3β) and peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α)/sirtuin 3 (SIRT3) pathways as potential avenues for halting neuroinflammation and oxidative stress in PD.
Aims: This study investigated for the first time the neuroprotective effect of canagliflozin against PD and LID in rotenone-intoxicated rats, emphasizing the crosstalk among the NLRP3/caspase-1 cascade, PGC-1α/SIRT3 pathway, mammalian target of rapamycin (mTOR)/beclin-1, and Nurr1/β-catenin/GSK-3β pathways as possible treatment strategies in PD and LID.
Brain Behav Immun
December 2024
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30322, USA; The Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, 30322. Electronic address:
Inflammatory biomarkers like C-reactive protein (CRP) are elevated in a subset of patients with depression and have been associated with lower functional connectivity (FC) in a ventral striatum (VS) to ventromedial prefrontal cortex (vmPFC) reward circuit and symptoms of anhedonia. Evidence linking these relationships to the effects of inflammation on dopamine is consistent with our recent findings that acute levodopa (L-DOPA) increased VS-vmPFC FC in association with deceased anhedonia in depressed patients with higher but not lower CRP (>2 versus ≤ 2 mg/L). To determine whether repeated L-DOPA administration caused sustained effects on FC and behavior in these patients, medically stable depressed outpatients with CRP > 2 mg/L and anhedonia (n = 18) received one week of three doses of L-DOPA (150-450 mg/day/week with carbidopa) or placebo in a randomized order.
View Article and Find Full Text PDFBehav Brain Res
March 2025
DELSU Joint Canada-Israel Neuroscience and Biopsychiatry Laboratory, Department of Pharmacology, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria.
Reducing antioxidant levels exacerbates the generation of reactive oxygen/nitrogen species, leading to alpha-synuclein aggregation and the degeneration of dopaminergic neurons. These play a key role in the onset of Parkinson's disease (PD), for which effective treatment remains elusive. This study examined the neuroprotective effects of taurine, an essential β-amino acid with antioxidant and antiinflammation properties, in Swiss male mice exposed to rotenone-induced PD.
View Article and Find Full Text PDFExpert Opin Drug Metab Toxicol
November 2024
Department of Neurology, St. Joseph Hospital Berlin-Weißensee, Berlin, Germany.
Introduction: Parkinson's disease is a chronic neurodegenerative disease entity characterized by heterogeneity of symptoms and progression. Levodopa is an efficacious and well tolerated dopamine substituting drug for its therapy. Its O-methylation and generation of 3-O-methyldopa is enhanced by levodopa/dopa decarboxylase inhibitor formulations.
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