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β‐Adrenergics enhance brain extraction of levodopa
Author(s) -
Uc Ergun Y.,
Dienel Gerald A.,
Cruz Nancy F.,
Harik Sami I.
Publication year - 2002
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.10002
Subject(s) - nadolol , adrenergic , agonist , endocrinology , medicine , chemistry , adrenergic agonist , levodopa , pharmacology , propranolol , parkinson's disease , receptor , disease
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.