MovDisordV3, PubMed, Corpus, bibRecord, 003B99

beta-Adrenergics enhance brain extraction of levodopa.

Identifieur interne : 003B99 ( PubMed/Corpus ); précédent : 003B98; suivant : 003C00

beta-Adrenergics enhance brain extraction of levodopa.

Auteurs : Ergun Y. Uc ; Gerald A. Dienel ; Nancy F. Cruz ; Sami I. Harik

Source :

Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2002.

RBID : pubmed:11835439

English descriptors

KwdEn :
- Adrenergic beta-Agonists (pharmacology), Adrenergic beta-Antagonists (pharmacology), Animals, Antiparkinson Agents (metabolism), Antiparkinson Agents (therapeutic use), Blood-Brain Barrier (drug effects), Brain (blood supply), Brain (drug effects), Cerebrovascular Circulation (physiology), Levodopa (metabolism), Levodopa (therapeutic use), Male, Parkinson Disease (drug therapy), Rats, Rats, Wistar.
MESH :
- chemical , metabolism : Antiparkinson Agents, Levodopa.
- chemical , pharmacology : Adrenergic beta-Agonists, Adrenergic beta-Antagonists.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa.
- blood supply : Brain.
- drug effects : Blood-Brain Barrier, Brain.
- drug therapy : Parkinson Disease.
- physiology : Cerebrovascular Circulation.
- Animals, Male, Rats, Rats, Wistar.

Abstract

We sought to determine whether beta-adrenergic agonists enhance the brain extraction of L-dopa and L-leucine. Systemic administration of beta-adrenergic agonists increase brain concentrations of L-dopa and other large neutral amino acids (LNAA) in rats and monkeys and may improve symptoms and reduce daily L-dopa requirement in patients with Parkinson's disease. Cerebral blood flow (CBF) using [3H]nicotine and the extraction fraction of 14C-labeled L-dopa or L-leucine were measured simultaneously in various brain regions of conscious rats using the dual-isotope indicator fractionation technique after intraperitoneal administration of isoproterenol (a peripheral nonselective beta-adrenergic agonist), or clenbuterol (a beta2-adrenergic agonist that crosses the blood-brain barrier), or beta-adrenergic agonist preceded by nadolol (a peripheral nonselective beta-adrenergic antagonist), or saline vehicle. Both beta-adrenergic agonists increased regional brain extraction fraction of L-dopa and L-leucine tracers by 35-45%, without altering regional CBF. These changes were accompanied by about a 30% decrease in plasma branched chain LNAA concentrations. Nadolol blocked all these effects. beta-Adrenergic agonists increase the brain extraction of L-dopa and leucine, mainly by peripheral mechanisms that reduce the levels of other competing plasma LNAAs for transport. Thus, beta-adrenergic agonists might be useful in the treatment of patients with Parkinson's disease by enhancing delivery of L-dopa to the brain.

PubMed: 11835439

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pubmed:11835439

Le document en format XML

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<author><name sortKey="Uc, Ergun Y" sort="Uc, Ergun Y" uniqKey="Uc E" first="Ergun Y" last="Uc">Ergun Y. Uc</name>
<affiliation><nlm:affiliation>Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. ergun-uc@uiowa.edu</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Dienel, Gerald A" sort="Dienel, Gerald A" uniqKey="Dienel G" first="Gerald A" last="Dienel">Gerald A. Dienel</name>
</author>
<author><name sortKey="Cruz, Nancy F" sort="Cruz, Nancy F" uniqKey="Cruz N" first="Nancy F" last="Cruz">Nancy F. Cruz</name>
</author>
<author><name sortKey="Harik, Sami I" sort="Harik, Sami I" uniqKey="Harik S" first="Sami I" last="Harik">Sami I. Harik</name>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">beta-Adrenergics enhance brain extraction of levodopa.</title>
<author><name sortKey="Uc, Ergun Y" sort="Uc, Ergun Y" uniqKey="Uc E" first="Ergun Y" last="Uc">Ergun Y. Uc</name>
<affiliation><nlm:affiliation>Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. ergun-uc@uiowa.edu</nlm:affiliation>
</affiliation>
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<author><name sortKey="Dienel, Gerald A" sort="Dienel, Gerald A" uniqKey="Dienel G" first="Gerald A" last="Dienel">Gerald A. Dienel</name>
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<author><name sortKey="Cruz, Nancy F" sort="Cruz, Nancy F" uniqKey="Cruz N" first="Nancy F" last="Cruz">Nancy F. Cruz</name>
</author>
<author><name sortKey="Harik, Sami I" sort="Harik, Sami I" uniqKey="Harik S" first="Sami I" last="Harik">Sami I. Harik</name>
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<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
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<term>Adrenergic beta-Antagonists (pharmacology)</term>
<term>Animals</term>
<term>Antiparkinson Agents (metabolism)</term>
<term>Antiparkinson Agents (therapeutic use)</term>
<term>Blood-Brain Barrier (drug effects)</term>
<term>Brain (blood supply)</term>
<term>Brain (drug effects)</term>
<term>Cerebrovascular Circulation (physiology)</term>
<term>Levodopa (metabolism)</term>
<term>Levodopa (therapeutic use)</term>
<term>Male</term>
<term>Parkinson Disease (drug therapy)</term>
<term>Rats</term>
<term>Rats, Wistar</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antiparkinson Agents</term>
<term>Levodopa</term>
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<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adrenergic beta-Agonists</term>
<term>Adrenergic beta-Antagonists</term>
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<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term>
<term>Levodopa</term>
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<keywords scheme="MESH" qualifier="blood supply" xml:lang="en"><term>Brain</term>
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<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Blood-Brain Barrier</term>
<term>Brain</term>
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<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term>
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<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Cerebrovascular Circulation</term>
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<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
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<front><div type="abstract" xml:lang="en">We sought to determine whether beta-adrenergic agonists enhance the brain extraction of L-dopa and L-leucine. Systemic administration of beta-adrenergic agonists increase brain concentrations of L-dopa and other large neutral amino acids (LNAA) in rats and monkeys and may improve symptoms and reduce daily L-dopa requirement in patients with Parkinson's disease. Cerebral blood flow (CBF) using [3H]nicotine and the extraction fraction of 14C-labeled L-dopa or L-leucine were measured simultaneously in various brain regions of conscious rats using the dual-isotope indicator fractionation technique after intraperitoneal administration of isoproterenol (a peripheral nonselective beta-adrenergic agonist), or clenbuterol (a beta2-adrenergic agonist that crosses the blood-brain barrier), or beta-adrenergic agonist preceded by nadolol (a peripheral nonselective beta-adrenergic antagonist), or saline vehicle. Both beta-adrenergic agonists increased regional brain extraction fraction of L-dopa and L-leucine tracers by 35-45%, without altering regional CBF. These changes were accompanied by about a 30% decrease in plasma branched chain LNAA concentrations. Nadolol blocked all these effects. beta-Adrenergic agonists increase the brain extraction of L-dopa and leucine, mainly by peripheral mechanisms that reduce the levels of other competing plasma LNAAs for transport. Thus, beta-adrenergic agonists might be useful in the treatment of patients with Parkinson's disease by enhancing delivery of L-dopa to the brain.</div>
</front>
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<Title>Movement disorders : official journal of the Movement Disorder Society</Title>
<ISOAbbreviation>Mov. Disord.</ISOAbbreviation>
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<ArticleTitle>beta-Adrenergics enhance brain extraction of levodopa.</ArticleTitle>
<Pagination><MedlinePgn>54-9</MedlinePgn>
</Pagination>
<Abstract><AbstractText>We sought to determine whether beta-adrenergic agonists enhance the brain extraction of L-dopa and L-leucine. Systemic administration of beta-adrenergic agonists increase brain concentrations of L-dopa and other large neutral amino acids (LNAA) in rats and monkeys and may improve symptoms and reduce daily L-dopa requirement in patients with Parkinson's disease. Cerebral blood flow (CBF) using [3H]nicotine and the extraction fraction of 14C-labeled L-dopa or L-leucine were measured simultaneously in various brain regions of conscious rats using the dual-isotope indicator fractionation technique after intraperitoneal administration of isoproterenol (a peripheral nonselective beta-adrenergic agonist), or clenbuterol (a beta2-adrenergic agonist that crosses the blood-brain barrier), or beta-adrenergic agonist preceded by nadolol (a peripheral nonselective beta-adrenergic antagonist), or saline vehicle. Both beta-adrenergic agonists increased regional brain extraction fraction of L-dopa and L-leucine tracers by 35-45%, without altering regional CBF. These changes were accompanied by about a 30% decrease in plasma branched chain LNAA concentrations. Nadolol blocked all these effects. beta-Adrenergic agonists increase the brain extraction of L-dopa and leucine, mainly by peripheral mechanisms that reduce the levels of other competing plasma LNAAs for transport. Thus, beta-adrenergic agonists might be useful in the treatment of patients with Parkinson's disease by enhancing delivery of L-dopa to the brain.</AbstractText>
<CopyrightInformation>Copyright 2001 Movement Disorder Society.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Uc</LastName>
<ForeName>Ergun Y</ForeName>
<Initials>EY</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. ergun-uc@uiowa.edu</Affiliation>
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<Author ValidYN="Y"><LastName>Cruz</LastName>
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<QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName>
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<QualifierName MajorTopicYN="Y" UI="Q000188">drug therapy</QualifierName>
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	Movement Disorders (revue)
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Movement Disorders (revue)

beta-Adrenergics enhance brain extraction of levodopa.

beta-Adrenergics enhance brain extraction of levodopa.

Source :

English descriptors

Abstract

Links to Exploration step

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