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Coadministration of β ‐asarone and levodopa increases dopamine in rat brain by accelerating transformation of levodopa: A different mechanism from M adopar
Author(s) -
Huang Liping,
Deng Minzhen,
Zhang Sheng,
Fang Yongqi,
Li Ling
Publication year - 2014
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12270
Subject(s) - homovanillic acid , benserazide , chemistry , dopamine , levodopa , pharmacology , striatum , monoamine oxidase , endocrinology , catechol o methyl transferase , saline , medicine , serotonin , parkinson's disease , biochemistry , enzyme , receptor , allele , disease , gene
Summary The aim of the present study was to investigate the effect of coadministration of β ‐asarone and levodopa ( l ‐dopa) on increasing dopamine ( DA ) in the striatum of healthy rats. Rats were randomly divided into four groups: (i) a normal group, administered normal saline; (ii) a Madopar group, administered 75 mg/kg Madopar ( l ‐dopa : benserazide, 4 : 1); (iii) an l ‐dopa group, administered 60 mg/kg l ‐dopa; and (iv) a group coadministered 15 mg/kg β ‐asarone and 60 mg/kg l ‐dopa. All drugs (or normal saline) were administered intragastrically twice a day for 7 days. Then, plasma and striatum concentrations of DA , l ‐dopa, 5‐hydroxytryptamine (5‐ HT ), homovanillic acid ( HVA ), 3,4‐dihydroxyphenylacetic acid ( DOPAC ), tyrosine hydroxylase ( TH ), catechol‐ O ‐methyltransferase ( COMT ) and monoamine oxidase B ( MAO ‐B) were determined. In the group coadministered β ‐asarone and l ‐dopa, there was a decline in plasma and striatal concentrations of l ‐dopa; however, DA and DOPAC concentrations increased in the striatum and plasma and plasma HVA concentrations increased, whereas there was no significant change in striatal levels. Concentrations of 5‐ HT in the striatum and plasma were similar in the coadministered and Madopar‐treated groups. In addition, plasma and striatal COMT levels decreased after coadministration of β ‐asarone and l ‐dopa, whereas there were no significant differences in MAO ‐ B concentrations among groups. Furthermore, coadministration of β ‐asarone and l ‐dopa increased plasma TH concentrations. Altogether, β ‐asarone affects the conversion of l ‐dopa to DA by modulating COMT activity and DA metabolism. The mechanism of coadministration is different from that of M adopar in P arkinson's disease ( PD ) treatment. Thus, the coadministration of β ‐asarone and l ‐dopa may be beneficial in the treatment of PD .