The effect of benserazide on the peripheral and central distribution and metabolism of levodopa after acute and chronic administration in the rat. |
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| Authors: | A P Kent G M Stern and R A Webster |
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| Affiliation: | Department of Pharmacology, University College, London. |
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| Abstract: | 1. The effects of levodopa alone (50 mg kg-1) and levodopa (10 mg kg-1) plus benserazide (50 mg kg-1) were tested on the levels of dopa, dopamine, 3-methoxytyrosine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), measured by h.p.l.c. with electrochemical detection, in samples of plasma, CSF, urine, striatum and hypothalamus of rats taken 30 min after injection. Levodopa plus benserazide produced significantly higher levels of dopa in plasma and brain than levodopa alone and reduced the peripheral synthesis and metabolism of dopamine. 2. When given chronically over 6 weeks the advantages of adding benserazide (50 mg kg-1 day-1) to levodopa (40 mg kg-1 day-1) were less marked and although more dopamine was present in the striatum than with levodopa given alone (200 mg kg-1 day-1) there was no evidence of any increase in its metabolites (HVA and DOPAC) and therefore of its turnover and utilisation. 3. The most striking effect of chronic treatment with levodopa plus benserazide was the appearance of large quantities of 3-MT in plasma, CSF and brain. 4. When levodopa alone, or levodopa plus benserazide, was given as an acute challenge to animals receiving the same treatment chronically, it was found that levodopa alone still produced increases in striatal dopamine, DOPAC and HVA in those animals dosed chronically on levodopa, but it was less effective in this respect when given with benserazide to the animals dosed with levodopa plus benserazide.(ABSTRACT TRUNCATED AT 250 WORDS) |
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