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

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.

Keywords: HPLC; dopamine; levodopa; plasma; striatum; β-asarone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / blood
  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Allylbenzene Derivatives
  • Animals
  • Anisoles / administration & dosage
  • Anisoles / pharmacology*
  • Benserazide / pharmacology*
  • Catechol O-Methyltransferase / blood
  • Catechol O-Methyltransferase / metabolism
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism*
  • Dopamine / blood
  • Dopamine / metabolism*
  • Dopamine Agents / pharmacology
  • Drug Combinations
  • Drug Interactions
  • Homovanillic Acid / blood
  • Homovanillic Acid / metabolism
  • Levodopa / administration & dosage
  • Levodopa / metabolism*
  • Levodopa / pharmacology*
  • Male
  • Monoamine Oxidase / metabolism
  • Rats
  • Serotonin / blood
  • Serotonin / metabolism
  • Tyrosine 3-Monooxygenase / blood
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Allylbenzene Derivatives
  • Anisoles
  • Dopamine Agents
  • Drug Combinations
  • asarone
  • benserazide, levodopa drug combination
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Levodopa
  • Benserazide
  • Tyrosine 3-Monooxygenase
  • Monoamine Oxidase
  • Catechol O-Methyltransferase
  • Dopamine
  • Homovanillic Acid