Pharmacokinetics of l-dopa in plasma and extracellular fluid of striatum in common marmosets

Zhang, Jie; Qu, Fang; Nakatsuka, Akiko; Nomura, Takuo; Nagai, Masahiro; Nomoto, Masahiro

doi:10.1016/j.brainres.2003.08.065

Cited by 28 publications

(11 citation statements)

References 29 publications

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“…5A). First of all, there was a very slow modification of baseline levels, which might be induced by oxidation of levodopa (i.e., its kinetic corresponds with that previously reported for levodopa) (Golembiowska and Dziubina, 2004;Marburger et al, 2000;Zhang et al, 2003), but which needs further study to be fully elucidated. Secondly, levodopa increased the amplitude of the amperometric response to MFB stimulation (Fig.…”

Section: Amperometrymentioning

confidence: 60%

“…In normal rats, peripheral administration of levodopa had a modest effect on the DA-pool studied by microdialysis (33-66 mg/kg induced no effect and 99-120 mg/kg only induced a modest 200% increase of DA). Bearing in mind that these doses are typically associated with a marked increment of brain levodopa levels (Abercrombie et al, 1990;Golembiowska and Dziubina, 2004;Marburger et al, 2000;Miller and Abercrombie, 1999;Zhang et al, 2003), the low DAresponse suggests that, under normal conditions, regulatory mechanisms handle extracellular DA very efficiently, thus preventing DA increases in nondenervated areas even when exposed to a high levodopa concentration. However, DA availability markedly increased (:600%) after DAergic denervation of the striatum, indicating a disruption of the normal regulation of extrasynaptic DA.…”

Section: Levodopa Action On the Microdialysismonitored Da-poolmentioning

confidence: 99%

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Different levodopa actions on the extracellular dopamine pools in the rat striatum

Rodrı́guez¹,

Moráles²,

González–Mora³

et al. 2006

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Levodopa has been the mainstay treatment for Parkinson's disease for several decades, but the precise mechanism for its therapeutic action is still not well understood. To date, little distinction has been made between the effects of levodopa on the different brain DA pools. We studied the levodopa action on two extracellular DA pools: one was analyzed by microdialysis (often considered as indicative of volume transmission) and the other by in vivo amperometry during nigrostriatal cell stimulation (more indicative of neurotransmission). Levodopa administration induced a moderate (increased 200%) and tardy (began at 60 min) increase in the DA-pool measured by microdialysis, an effect that increased (increased 500%) and accelerated (began at 10 min) after DA-cell degeneration. Levodopa action on the DA-pool measured by amperometry was very fast (10 min) and prominent (increased 600%) in normal rats. The DA-denervated striatum showed a fast exhaustion during cell stimulation, which prevented further study of the levodopa effect on the DA amperometry-pool under this condition. This study suggests a different kinetic for levodopa action on the volume transmitter and neurotransmitter DA-pool, showing marked changes in levodopa action in the denervated striatum.

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Section: Amperometrymentioning

confidence: 60%

Section: Levodopa Action On the Microdialysismonitored Da-poolmentioning

confidence: 99%

Different levodopa actions on the extracellular dopamine pools in the rat striatum

Rodrı́guez¹,

Moráles²,

González–Mora³

et al. 2006

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“…Bioavailability of l ‐DOPA was an obvious control as l ‐DOPA is the gold‐standard treatment of PD and is the reference therapeutic in virtually all preclinical experiments aiming at validating new therapeutic strategies (Meissner et al, ). Few studies had previously assessed the pharmacokinetics of l ‐DOPA in the nonhuman primate (Alexander et al, ; Cao et al, ; Hammerstad and Calne, ; Hammerstad et al, ; Huot et al, ; Zhang et al, ). To the best of our knowledge, only one study was performed in parkinsonian nonhuman primates with oral route dosing and CSF sampling (Huot et al, ).…”

Section: Discussionmentioning

confidence: 99%

Permeability of blood–brain barrier in macaque model of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced Parkinson disease

Thiollier

Contamin³

et al. 2016

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Brain bioavailability of drugs developed to address central nervous system diseases is classically documented through cerebrospinal fluid collected in normal animals, i.e., through an approximation as there are fundamental differences between cerebrospinal fluid and tissue contents. The fact that disease might affect brain availability of drugs is almost never considered at this stage although several conditions are associated with blood-brain barrier damage. Building upon our expertise in Parkinson's disease translational research, the present study addressed this gap comparing plasma and cerebrospinal fluid bioavailability of l-3,4-dihydroxyphenylalanine, carbamazepine, quinidine, lovastatin, and simvastatin, in healthy and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated macaques, the gold standard model of Parkinson's disease. The drugs were selected based upon their differential transport across the blood-brain barrier. Interestingly, brain bioavailability of quinidine was decreased while others were unaffected. Pharmacokinetics and pharmacodynamics experiments of drugs addressing Parkinson's disease might thus be performed in healthy animals unless the drugs are known to interact with the organic cation transporter.

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“…The analysis is performed in fresh brain samples, cerebrospinal fluid or extracellular fluid obtained by in vivo microdialysis (e.g. : Emborg et al, 2001;Zhang et al, 2003). Concentration of monoamines is calculated by comparing the electrochemical signal of each sample to a known set of standards that contained each of the monoamines and their metabolites.…”

Section: Catecholamine Biochemistrymentioning

confidence: 99%

Evaluation of animal models of Parkinson's disease for neuroprotective strategies

Emborg

2004

Journal of Neuroscience Methods

142

123

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Pharmacokinetics of l-dopa in plasma and extracellular fluid of striatum in common marmosets

Cited by 28 publications

References 29 publications

Different levodopa actions on the extracellular dopamine pools in the rat striatum

Different levodopa actions on the extracellular dopamine pools in the rat striatum

Permeability of blood–brain barrier in macaque model of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced Parkinson disease

Evaluation of animal models of Parkinson's disease for neuroprotective strategies

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