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β-细辛醚与左旋多巴联合给药通过加速左旋多巴的转化增加大鼠脑内多巴胺:一种不同于美多芭的作用机制。

Coadministration of β-asarone and levodopa increases dopamine in rat brain by accelerating transformation of levodopa: a different mechanism from Madopar.

作者信息

Huang Liping, Deng Minzhen, Zhang Sheng, Fang Yongqi, Li Ling

机构信息

The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Clin Exp Pharmacol Physiol. 2014 Sep;41(9):685-90. doi: 10.1111/1440-1681.12270.

Abstract

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 Madopar in Parkinson's disease (PD) treatment. Thus, the coadministration of β-asarone and l-dopa may be beneficial in the treatment of PD.

摘要

本研究的目的是探讨β-细辛醚与左旋多巴(L-多巴)联合给药对增加健康大鼠纹状体中多巴胺(DA)的影响。大鼠被随机分为四组:(i)正常组,给予生理盐水;(ii)美多芭组,给予75mg/kg美多芭(L-多巴:苄丝肼,4:1);(iii)L-多巴组,给予60mg/kg L-多巴;(iv)联合给予15mg/kgβ-细辛醚和60mg/kg L-多巴的组。所有药物(或生理盐水)每天经胃内给药两次,共7天。然后,测定血浆和纹状体中DA、L-多巴、5-羟色胺(5-HT)、高香草酸(HVA)、3,4-二羟基苯乙酸(DOPAC)、酪氨酸羟化酶(TH)、儿茶酚-O-甲基转移酶(COMT)和单胺氧化酶B(MAO-B)的浓度。在联合给予β-细辛醚和L-多巴的组中,血浆和纹状体中L-多巴的浓度下降;然而,纹状体和血浆中DA和DOPAC的浓度增加,血浆HVA浓度增加,而纹状体水平无显著变化。联合给药组和接受美多芭治疗组的纹状体和血浆中5-HT的浓度相似。此外,联合给予β-细辛醚和L-多巴后,血浆和纹状体中的COMT水平下降,而各组间MAO-B浓度无显著差异。此外,联合给予β-细辛醚和L-多巴可提高血浆TH浓度。总之,β-细辛醚通过调节COMT活性和DA代谢影响L-多巴向DA的转化。联合给药的机制与帕金森病(PD)治疗中美多芭的机制不同。因此,β-细辛醚与L-多巴联合给药可能对PD治疗有益。

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