title: Coadministration of β-asarone and levodopa increases dopamine in rat brain by accelerating transformation of levodopa: a different mechanism from Madopar.
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.
authors.affiliation: The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.forename: Minzhen
authors.initials: M
authors.lastname: Deng
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Fang
authors.forename: Ling
authors.initials: L
authors.lastname: Li
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000097:blood / Q000378:metabolism; D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage / Q000494:pharmacology*; D001545:Benserazide / Q000494:pharmacology*; D002394:Catechol O-Methyltransferase / Q000097:blood / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000097:blood / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004338:Drug Combinations; D004347:Drug Interactions; D006719:Homovanillic Acid / Q000097:blood / Q000378:metabolism; D007980:Levodopa / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000097:blood / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000097:blood / Q000378:metabolism
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D015259:Dopamine Agents; D004338:Drug Combinations; C012195:asarone; C005177:benserazide, levodopa drug combination; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D007980:Levodopa; D001545:Benserazide; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D004298:Dopamine; D006719:Homovanillic Acid
keywords: HPLC; dopamine; levodopa; plasma; striatum; β-asarone