Peripheral aromatic <scp>l</scp>‐amino acids decarboxylase inhibitor in parkinsonism. II. Effect on metabolism of <scp>l</scp>‐2‐<sup>14</sup>C‐dopa

Bianchine, Joseph R.; Messiha, F.S.; Hsu, Tah-Hsiung

doi:10.1002/cpt1972134584

Cited by 25 publications

(15 citation statements)

References 6 publications

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“…Moreover, we have found that administration of pyridoxine during treatment with levodopa and carbidopa (MK-486) to two Parkinsonian patients, initially decreased the excretion of levodopa major metabolites and thus failed to increase the same as without carbidopa (18). The latter exert an inhibitory effect on extracerebral decarboxylation of levodopa ( 19,20). All these findings are compatible with the postulate that pyridoxine enhances or accelerates the decarboxylation of DOPA to DA and may explain the mechanism by which pyridoxine negates the therapeutic efficacy of levodopa.…”

supporting

confidence: 63%

Effect of Pyridoxine on Levodopa Metabolism in Normal and Parkinsonian Subjects

Hsu¹,

Bianchine²,

Preziosi³

et al. 1973

Experimental Biology and Medicine

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A high frequency of dose-dependent side effects aften limits the therapeutic efficacy of Levodopa (L-DOPA) in the treatment of Parkinson's Disease (1). Inhibitors of peripheral aromatic L-amino acids decarbosylase have been utilized experimentally as adjunct therapy to L-DOPA in Parkinson's Disease (2-7). These inhibitors decrease the dose requirements of L-DOPA and certain side effects such as nausea and vomiting but do not alter the incidence of dyskinesias ( 2 , 3 , 5-7). Paradoxically, co-administration of pyridoxine with L-DOP,~ negates the therapeutic effect of L-DOPA (8: 9) but improves dopa-induced dyskinesia. Pyridoxine which is converted to pyridoxal 5-phosphate (vitamin BB) a cofactor for enzymatic decarboxylation and transamination of aromatic L-amino acids, may accelerate metabolism of L-DOPA. To test this possibility, we studied the effect of pyridoxine administration on urinary excretion of DOPA and certain DOPA metabolites following administration of L-DOPA to normal and Parkinsonian subjects.Material and Methods. ( a ) Clinical. Five consenting Parkinsonian patients, uncomplicated by cardiac, renal or hepatic disease, were admitted to the metabolic ward. These patients, ages 57-76, had been treated with L-DOPA, 3-6 g/day, during the previous two years. Their L-DOPA treatment was reduced to 2 g daily (0.5 g each 2 hr beginning a t 8 AM) for seven days prior to pyridoxine administration. On Days 8 and 9, L-DOPA was continued at 2 g daily and pyridoxine was administered by mouth 50 mg each 4 hr beginning at 8 AM for a total daily dose of 150 mg. On Days 7 and 9, total urine output was collected serially, over acid, a t 2, 4, 6, 8, and 24 hr.Four healthy consenting volunteer men, ages 2 9-42, received progressively increased oral doses of L-DOPA from 0.5 to 2.0 g daily for seven consecutive days. On Days 8-15, oral L-DOPA was continued, 0.5 g at 2-hr intervals, beginning at 8 AM for a total daily dose of 2 .O g. On Days 14 and 15, pyridoxine was administered by mouth, 50 mg each 4 hr, for a total daily dose of 150 mg. On Days 13 and 15, urine was collected serially as described above, All urine specimens were collected in dark glass containers over 6 N hydrochloric acid.( b ) Chemical analyses. Urine samples were kept frozen at -20' until chemical analyses were made. The fractionation of urinary dopa and selected metabolites, i.e., dopamine (DA) , dihydroxyphenylacetic acid (DOPAC) , homovanillic acid (HVA) , were pedormed as previously described (10). The quantitative determination of DOPA, DA, DOPAC, and HVA utilized spectrofluorimetric methods (10-13). VMA was determined by the procedure of Pisano et al. (14). Data for DOPA and DA are given for hydrolyzed urine specimens and include both free and conj uga t es.Results. The effects of pyridoxine administration on the urinary excretion of DOPA, DA, DOPAC, and HVA for the group of 5 Parkinsonian subjects are summarized in Table I. The data are expressed as Mean * SD and are analyzed by t test for correlated means. Simultaneous administration of pyrid...

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supporting

confidence: 63%

Effect of Pyridoxine on Levodopa Metabolism in Normal and Parkinsonian Subjects

Hsu¹,

Bianchine²,

Preziosi³

et al. 1973

Experimental Biology and Medicine

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“…The impact of decarboxylase inhibitors on latency to peak concentrations varies in the reported literature. This has been found to be either shorter, 26 similar, 10 12 29 or longer 9 compared with L-dopa alone, and one study 28 found a dose-dependent reduction in T max in the presence of CD. Although the delay to maximum plasma concentration of 95.5 min found in our study appears rather long, similar delays on standard release LD/decarboxylase inhibitor have been reported in the literature.…”

Section: Discussionmentioning

confidence: 99%

Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

Katzenschlager

Evans²,

Manson³

et al. 2004

Journal of Neurology, Neurosurgery & Psychiatry

245

138

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Background: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (L-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard L-dopa/carbidopa (LD/CD). Methods: Eight Parkinson's disease patients with a short duration L-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial. Patients were challenged with single doses of 200/50 mg LD/CD, and 15 and 30 g of mucuna preparation in randomised order at weekly intervals. L-Dopa pharmacokinetics were determined, and Unified Parkinson's Disease Rating Scale and tapping speed were obtained at baseline and repeatedly during the 4 h following drug ingestion. Dyskinesias were assessed using modified AIMS and Goetz scales. Results: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak L-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak L-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. Conclusions: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted.

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“…Orally administered levodopa is 95% metabolized outside the brain (Bianchine et al, 1972). The major metabolic pathway is by decarboxylation.…”

Section: Resultsmentioning

confidence: 99%

Plasma Dopa Concentrations After Different Preparations of Levodopa in Normal Subjects

Morris

Parsons

Trounce

et al. 1976

Brit J Clinical Pharma

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I The concurrent administration of levodopa with a decarboxylase inhibitor produced a plasma concentration/time curve comparable with 1/4 to 1/5 of the dose of levodopa given alone. 2 There was no evidence to suggest that the decarboxylase inhibitor slowed the rate of elimination of levodopa from plasma. 3 Metoclopramide (Maxolon) increased the rate of levodopa absorption. Higher plasma concentrations of levodopa during the first 2 h after dosing were followed by lower plasma concentrations during the third and fourth hours. The amount of levodopa absorbed after Larodopa as indicated by the AUC was not altered by adding metoclopramide. 4 None of the current preparations of levodopa produced sustained plasma concentrations. 5In vitro testing confirmed that Brocadopa Temtabs tablets disintegrate and dissolve slowly. In vivo, Brocadopa Temtabs behaved as a slow release preparation but it did not produce sustained plasma concentrations of levodopa.

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Peripheral aromatic l‐amino acids decarboxylase inhibitor in parkinsonism. II. Effect on metabolism of l‐2‐¹⁴C‐dopa

Cited by 25 publications

References 6 publications

Effect of Pyridoxine on Levodopa Metabolism in Normal and Parkinsonian Subjects

Effect of Pyridoxine on Levodopa Metabolism in Normal and Parkinsonian Subjects

Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

Plasma Dopa Concentrations After Different Preparations of Levodopa in Normal Subjects

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Peripheral aromatic l‐amino acids decarboxylase inhibitor in parkinsonism. II. Effect on metabolism of l‐2‐14C‐dopa

Cited by 25 publications

References 6 publications

Effect of Pyridoxine on Levodopa Metabolism in Normal and Parkinsonian Subjects

Effect of Pyridoxine on Levodopa Metabolism in Normal and Parkinsonian Subjects

Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

Plasma Dopa Concentrations After Different Preparations of Levodopa in Normal Subjects

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Peripheral aromatic l‐amino acids decarboxylase inhibitor in parkinsonism. II. Effect on metabolism of l‐2‐¹⁴C‐dopa