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β-Adrenergics enhance brain extraction of levodopa

✍ Scribed by Ergun Y. Uc; Gerald A. Dienel; Nancy F. Cruz; Sami I. Harik

Publisher
John Wiley and Sons
Year
2001
Tongue
English
Weight
156 KB
Volume
17
Category
Article
ISSN
0885-3185

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

We sought to determine whether β‐adrenergic agonists enhance the brain extraction of L‐dopa and L‐leucine. Systemic administration of β‐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 [^3^H]nicotine and the extraction fraction of ^14^C‐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 β‐adrenergic agonist), or clenbuterol (a β~2~‐adrenergic agonist that crosses the blood–brain barrier), or β‐adrenergic agonist preceded by nadolol (a peripheral nonselective β‐adrenergic antagonist), or saline vehicle. Both β‐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. β‐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, β‐adrenergic agonists might be useful in the treatment of patients with Parkinson's disease by enhancing delivery of L‐dopa to the brain. © 2001 Movement Disorder Society.

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